- PYRAZOLYLACYLPYRAZOLINE COMPOUNDS AND METHOD FOR TREATING PAIN
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This invention relates to pyrazolylacylpyrazoline compounds or pharmaceutically acceptable salts thereof, and for the use of the compounds to treat neurological disorders.
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Paragraph 0172; 0200
(2021/05/29)
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- Synthesis and Anti-Proliferative Activity of New α-Amino Phosphonate Derivatives Bearing Heterocyclic Moiety
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Condensation of 4-chloroacetophenone 1 with phenyl hydrazine 2 afforded hydrazone 3. Further reaction of 3 with Vilsmeier reagent yielded the pyrazolaldehyde 4 in excellent yield. A one-pot, three-component reaction between aldehyde 4, triphenylphosphite 5, and appropriate amines in the presence of lithium perchlorate as Lewis acid catalyst gave the corresponding α-amino phosphonates 7-12(a-d) in good yields. The chemical structures of all new compounds were established by IR, 1H NMR, and mass spectroscopy analysis. The anti-proliferative activity of the synthesized compounds against HCT-116, HepG2 and MCF-7 human cancer cells using the MTT assay was evaluated, and revealed higher anticancer activity when compared with reference drug doxorubicin. Among the tested compounds, pyrazole derivatives 4 and 9 exhibited the highest anticancer activity against breast (MCF-7), and colon (HCT-116) cancer cell lines with IC50 = 2.7 and 3.3 μM, respectively.
- Abdelwahed, Ramzy E.,Awad, Hanem M.,El Gokha, Ahmed A.,El Sayed, Ibrahim El-Tantawy,Goda, Adel E-S.,Radhi, Ahmed Habeeb
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- Design and synthesis of pyrazole–pyrazoline hybrids as cancer-associated selective COX-2 inhibitors
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In continuation of our previous work on cancer and inflammation, 15 novel pyrazole–pyrazoline hybrids (WSPP1–15) were synthesized and fully characterized. The formation of the pyrazoline ring was confirmed by the appearance of three doublets of doublets in 1H nuclear magnetic resonance spectra exhibiting an AMX pattern for three protons (HA, HM, and HX) of the pyrazoline ring. All the synthesized compounds were screened for their in vitro anticancer activity against five cell lines, that is, MCF-7, A549, SiHa, COLO205, and HepG2 cells, using the MTT growth inhibition assay. 5-Fluorouracil was taken as the positive control in the study. It was observed that, among them, WSPP11 was found to be active against A549, SiHa, COLO205, and HepG2 cells, with IC50 values of 4.94, 4.54, 4.86, and 2.09 μM. All the derivatives were also evaluated for their cytotoxicity against HaCaT cells. WSPP11 was also found to be nontoxic against normal cells (cell line HaCaT), with an IC50 value of more than 50 μM. The derivatives were also evaluated for their in vitro anti-inflammatory activity by the protein (egg albumin) denaturation assay and the red blood cell membrane stabilizing assay, using diclofenac sodium and celecoxib as standard. Compounds that showed significant anticancer and anti-inflammatory activities were further studied for COX-2 inhibition. The manifestation of a higher COX-2 selectivity index of WSPP11 as compared with other derivatives and an in vitro anticancer activity against four cell lines further established that compounds that were more selective toward COX-2 also exhibited a better spectrum of activity against various cancer cell lines.
- Akhtar, Wasim,Marella, Akranth,Alam, Mohammad Mumtaz,Khan, Mohemmed F.,Akhtar, Mymoona,Anwer, Tariq,Khan, Farah,Naematullah, Md.,Azam, Faizul,Rizvi, Moshahid A.,Shaquiquzzaman, Mohammad
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- Design and synthesis of novel pyrazole-phenyl semicarbazone derivatives as potential α-glucosidase inhibitor: Kinetics and molecular dynamics simulation study
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A series of novel pyrazole-phenyl semicarbazone derivatives were designed, synthesized, and screened for in vitro α-glucosidase inhibitory activity. Given the importance of hydrogen bonding in promoting the α-glucosidase inhibitory activity, pharmacophore modification was established. The docking results rationalized the idea of the design. All newly synthesized compounds exhibited excellent in vitro yeast α-glucosidase inhibition (IC50 values in the range of 65.1–695.0 μM) even much more potent than standard drug acarbose (IC50 = 750.0 μM). Among them, compounds 8o displayed the most potent α-glucosidase inhibitory activity (IC50 = 65.1 ± 0.3 μM). Kinetic study of compound 8o revealed that it inhibited α-glucosidase in a competitive mode (Ki = 87.0 μM). Limited SAR suggested that electronic properties of substitutions have little effect on inhibitory potential of compounds. Cytotoxic studies demonstrated that the active compounds (8o, 8k, 8p, 8l, 8i, and 8a) compounds are also non-cytotoxic. The binding modes of the most potent compounds 8o, 8k, 8p, 8l and 8i was studied through in silico docking studies. Molecular dynamic simulations have been performed in order to explain the dynamic behavior and structural changes of the systems by the calculation of the root mean square deviation (RMSD) and root mean square fluctuation (RMSF).
- Azimi, Fateme,Ghasemi, Jahan B.,Azizian, Homa,Najafi, Mohammad,Faramarzi, Mohammad Ali,Saghaei, Lotfollah,Sadeghi-aliabadi, Hojjat,Larijani, Bagher,Hassanzadeh, Farshid,Mahdavi, Mohammad
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p. 1082 - 1095
(2020/11/20)
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- Synthesis, characterization and antibacterial evaluation of 2, 3dihydroquinazolin-4 (1h)-ones and some new bis 2, 3-dihydroquinazolin-4 (1h)-ones using pre-made pyrazole carbaldehyde derivatives
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2, 3-Dihydroquinazolinones are of popular compounds with the diversification of biological and pharmacological activities. Among many discovered methods, there are efficient and convenient methods used for the synthesis of 2, 3-dihydroquinazoline-4 (1H)-one and some new bis 2, 3-dihydroquinazoline-4 (1H)-one derivatives which are reported in this study. The mentioned methods include the two-component condensation of one molecule of anthranilamide and one molecule of pyra-zole carbaldehyde using montmorillonite-K10 as a catalyst for the preparation of 2, 3 dihydroquinazo-line-4 (1H)-ones. Also, one-pot pseudo-five-component reaction (5MCRs) of two molecules of isatoic anhydride, two molecules of pyrazole carbaldehydes and one molecule of ethan-1, 2-diamine in the presence of the r catalyst (montmorillonite-K10) for the synthesis of bis 2, 3-dihydroquinazoline-4 (1H)-ones. Despite the short times of reactions, high yields of products were obtained, which were val-idated using FT-IR,1HNMR,13CNMR, and elemental analysis. Moreover, the compounds were screened for their antimicrobial activities against two-gram-positive bacterial strains: Staphylococcus aureus and Micrococcus Luteus; and against two-gram-negative bacterial strains, as well: Escherichia coli and Pseudomonas aeruginosa, which all were utilized for antibacterial investigations. The results showed moderate or significant antibacterial activities.
- Mahmoodi, Nosrat Ollah,Sina, Kiana Faraji,Yahyazadeh, Asieh
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p. 176 - 182
(2021/03/19)
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- Synthesis, Characterization, and Biological Evolution of New Pyrazole Derivatives of 4-(4-Aminophenyl)morpholin-3-one through Ugi Reaction
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A new heterocyclic library was synthesized using multicomponent reactions (MCRs). A green strategy during which a set of molecules with an excellent diversity is generated with a minimum of synthetic effort, time, and by-products formation. This new series prepared using the Ugi MCRs in which aldehyde, amine, acid, and isocyanide reacts to make α-bisamide. During this work, we practice the Ugi reaction to synthesize an extremely functionalized heterocyclic library which was characterized and tested for biological evaluation. This innovative synthetic route involves for pyrazole derivatives of 4-(4-aminophenyl)morpholin-3-one by Ugi four component reaction and methanol as a solvent in good yield and high purity. All the produced compounds of library were characterized using 1H-NMR, IR, and mass spectroscopic methods.
- Joshi, Harsh H.,Parsania, M. V.
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p. 247 - 253
(2021/08/03)
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- Design, synthesis, biological evaluation, and molecular docking studies of some novel N,N-dimethylaminopropoxy-substituted aurones
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In continuation of our ongoing research on the discovery of novel and potentially bioactive aurones, we have designed and synthesized some novel N,N-dimethylaminopropoxy-substituted pyrazole-based aurones 10(a-l). These pyrazole-benzofuranone hybrid compounds were characterized by using their IR, 1H-NMR, 13C-NMR, and mass spectrometry data. Compound 10c was used as a model to further explicate the structure of tilted compounds by means of 1H-1H COSY, 1H-13C HMQC, 1H-13C HMBC, 1H-1H TOCSY, 1H-1H NOSEY, DEPT-45°, DEPT-90°, and DEPT-135° NMR spectra. The comparative molecular docking study of N,N-dimethylaminopropoxy-substituted pyrazole-based aurones and standard drugs (Ampicillin and Chloramphenicol) against Bacillus subtilis (PDB: 6tzp) active site was performed to determine the binding interactions, binding energy, and orientation of the molecules at the active site of the target protein. Out of these synthesized compounds, five best analogs (10b, 10f, 10h, 10k, and 10l) of docking results were also evaluated for their in vitro antibacterial potential against Bacillus subtilis to validate the docking results.
- Dalal, Sunita,Kumar, Gourav,Kumar, Ramesh,Kumar, Suresh,Kumari, Meena,Saroha, Bhavna
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- H3PO4 catalyzed one-pot synthesis of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde to novel 1,3-diphenyl-1H-pyrazole-4-carbonitrile
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Abstract: One-pot condensation of pyrazole-4-aldehydes and hydroxylamine hydrochloride to form the corresponding oxime using formic acid as a medium and further dehydration of oxime using a catalytic amount of orthophosphoric acid to afford novel pyrazole-4-carbonitrile. This protocol serves as an ortho-phosphoric acid-catalyzed one-pot conversion of aldehyde to nitrile. Most remarkable features of this method are metal-free, cost-effective, atom efficiency with excellent yield (98–99%). This process will serve as a robust and scalable tool for the synthesis of valuable and versatile precursor (nitriles). This precursor will pave the way for the synthesis of various medicinally important valuable compounds. Graphic abstract: [Figure not available: see fulltext.].
- Choudhare, Tukaram S,Netankar, Prashant D,Shirsath, Sagar E,Wagare, Devendra S
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- Design and synthesis of novel quinazolinone-pyrazole derivatives as potential α-glucosidase inhibitors: Structure-activity relationship, molecular modeling and kinetic study
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In this study, a new series of quinazolinone-pyrazole hybrids were designed, synthesized and screened for their α-glucosidase inhibitory activity. The results of the in vitro screening indicated that all the molecular hybrids exhibited more inhibitory activity (IC50 values ranging from 60.5 ± 0.3 μM-186.6 ± 20 μM) in comparison to standard acarbose (IC50 = 750.0 ± 10.0 μM). Limited structure–activity relationship suggested that the variation in the inhibitory activities of the compounds affected by different substitutions on phenyl rings of diphenyl pyrazole moiety. The enzyme kinetic studies of the most potent compound 9i revealed that it inhibited α-glucosidase in a competitive mode with a Ki of 56 μM. Molecular docking study was performed to predict the putative binding interaction. As expected, all pharmacophoric moieties used in the initial structure design playing a pivotal role in the interaction with the binding site of the enzyme. In addition, by performing molecular dynamic investigation and MM-GBSA calculation, we investigated the difference in structural perturbation and dynamic behavior that is observed over α-glycosidase in complex with the most active compound and acarbose relative to unbound α-glycosidase enzyme.
- Azimi, Fateme,Azizian, Homa,Najafi, Mohammad,Hassanzadeh, Farshid,Sadeghi-aliabadi, Hojjat,Ghasemi, Jahan B.,Ali Faramarzi, Mohammad,Mojtabavi, Somayeh,Larijani, Bagher,Saghaei, Lotfollah,Mahdavi, Mohammad
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- Synthesis, XRD, characterization and antibacterial activity of novel α,β unsaturated carbonyl compound: (Z)-2-((3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-3,4-dihydronaphthalen-1(2H)-one (C26H19ClN2O)
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A novel organic α,β unsaturated carbonyl compound (Z)-2-((3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-3,4-dihydronaphthalen-1(2H)-one (K) was Synthesized through Ultrasound Irradiation by the help of green solvent and grown a high quality single crystal by slow evaporation method. Structural confirmation was carried out by most acceptable spectroscopic techniques i.e. MS, IR, NMR, CMR, DSC, Crystal Structure of K was determined by single crystal X-ray Diffraction. The single crystal of K was developed in 0.40 × 0.35 × 0.30 mm dimension in EtOH:Acetone (1:2) solvent system. K crystallizes in the monoclinic crystal class in the asymmetrical space group with Z = 4. Potency of compound was assayed against four bacterial microorganisms.
- Bhola, Yogesh O.,Dodeja, Khushbu K.,Naliapara, Y. T.
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- Highly efficient one-pot synthesis of α-aminophosphonates using nanoporous AlSBA-15 catalyst in a three-component system
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Nanoporous AlSBA-15 catalysts with different nSi/nAl ratios (41, 129, and 210) were synthesized using a hydrothermal method. These catalysts were characterized by XRD, N2 sorption, TPD-NH3, FT-IR, SEM and TEM. XRD analyses of AlSBA-15 catalysts confirmed the presence of well-ordered crystalline structure with p6mm symmetry. The specific surface area and specific pore volume of the AlSBA-15 catalysts are in the range of 480 to 757?m2/g and 0.65 to 0.95?cm3/g, respectively. The catalytic performance of nanoporous AlSBA-15 catalysts are used as an outstanding catalytic system for one-pot synthesis of α-aminophosphonates via Kabachnik-Fields reaction in a three-component system using amines (primary/secondary), carbonyl compounds (aldehydes/ketones) and diethyl phosphite. The major advantages of the present contributions are excellent yields, short reaction time, simple experimental technique, high chemo-selectivity, catalyst recyclability, easy work-up procedure and green approach. Three-component synthesis of α-aminophosphonates follows first imine formation from amine and aldehyde/ketone followed by phosphate addition. The experimental findings suggest that the nanoporous AlSBA-15 catalysts can be recycled and reused up to six cycles without any loss in the catalytic performance.
- Kolli, Murali Krishna,Palani, Elamathi,Govindasamy, Chandrasekar,Katta, Vishweshwar Rao
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p. 1047 - 1064
(2018/10/31)
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- New library of pyrazole–imidazo[1,2-α]pyridine molecular conjugates: Synthesis, antibacterial activity and molecular docking studies
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A library of novel pyrazole–imidazo[1,2-α]pyridine scaffolds was designed and synthesized through a one-pot three-component tandem reaction. The structures of synthesized conjugates were confirmed by spectroscopic techniques (NMR, IR and HRMS). In vitro antibacterial evaluation of the twelve synthesized molecules (7a, 8a–k) against methicillin-resistant Staphylococcus aureus and normal strains of Escherichia coli, Salmonella typhimurium, Klebsiella pneumonia and Pseudomonas aeruginosa established 8b, 8d, 8e, 8h and 8i as potent antibacterial agents with superior minimum bactericidal concentration, compared with standard drug ciprofloxacin. Molecular docking studies of all active compounds into the binding site of glucosamine-6-phosphate synthase were further performed in order to have a comprehensive understanding of putative binding modes within the active sites of the receptor.
- Ebenezer, Oluwakemi,Awolade, Paul,Koorbanally, Neil,Singh, Parvesh
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p. 162 - 173
(2019/11/03)
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- In vitro studies of potent aldose reductase inhibitors: Synthesis, characterization, biological evaluation and docking analysis of rhodanine-3-hippuric acid derivatives
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Inhibitors of aldose reductase are rate-limiting enzymes and could play a key role to prevent the complications of diabetes. In our attempt to develop novel inhibitors of aldose reductase, the derivatives of rhodanine-3-hippuric acid-pyrazole hybrid were synthesized and characterised by spectral data. The biological studies reveal that all the compounds show an excellent activity against ALR2 with IC50 values ranging from 0.04 to 1.36 μM. Among these the synthesised compounds 6a-m, 6g and 6e showed specific inhibitory activity with IC50 values of 0.04 and 0.06 μM respectively against ALR2 and found to be more potent than epalrestat (IC50 = 0.87 μM), the only aldose reductase inhibitor currently used in the therapy. Molecular docking analysis using the AR-NADP+ complex as a receptor was performed with all the synthesized compounds. All the compounds exhibit a well-defined binding mode within the AR active site, similarly to previous described AR inhibitors, with the anion head group bound to the catalytic center, blocking thus its activity. By forming hydrogen bonds with Tyr48 and His110 of the protein from ALR2 (PDB ID: 2FZD), the compounds 6g and 6e interrupt the proton donation mechanism, which is necessary for the catalytic activity of ALR2.
- Celestina, Stephen Kumar,Ravi, Subban,Sundaram, Kaveri
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- Discovery of pyrazole derivatives as cellular active inhibitors of histone lysine specific demethylase 5B (KDM5B/JARID1B)
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KDM5B (also known as PLU-1 and JARID1B) is 2-oxoglutarate and Fe2+ dependent oxygenase that acts as a histone H3K4 demethylase, which is a key participant in inhibiting the expression of tumor suppressors as a drug target. Here, we present the discovery of pyrazole derivatives compound 5 by structure-based virtual screening and biochemical screening with IC50 of 9.320 μM against KDM5B, and its subsequent optimization to give 1-(4-methoxyphenyl)-N-(2-methyl-2-morpholinopropyl)-3-phenyl-1H-pyrazole-4-carboxamide (27 ab), a potent KDM5B inhibitor with IC50 of 0.0244 μM. In MKN45 cells, compound 27 ab can bind and stabilize KDM5B and induce the accumulation of H3K4me2/3, bona fide substrates of KDM5B, while keep the amount of H3K4me1, H3K9me2/3 and H3K27me2 without change. Further biological study also indicated that compound 27 ab is a potent cellular active KDM5B inhibitor that can inhibit MKN45 cell proliferation, wound healing and migration. In sum, our finding gives a novel structure for the discovery of KDM5B inhibitor and targeting KDM5B may be a new therapeutic strategy for gastric cancer treatment.
- Liang, Qianqian,Liu, Hong-Min,Ma, Li-Ying,Ren, Hongmei,Wu, Yang,Zhang, Kun,Zhang, Xinhui,Zhao, Bing,Zheng, Yi-Chao
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- Synthesis and computational studies of highly selective inhibitors of human recombinant tissue non-specific alkaline phosphatase (h-TNAP): A therapeutic target against vascular calcification
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In this study, we have discovered small druglike molecules as selective inhibitors of human tissue-nonspecific alkaline phosphatase (h-TNAP), an enzyme critical for the regulation of extracellular matrix calcification. The upregulation of h-TNAP is associated with various pathologies particularly the vascular calcification (VC). Selective inhibition of h-TNAP over h-NPP1 may serve as a useful therapeutic strategy against vascular calcification. A series of novel triazolyl pyrazole derivatives (10a-y) in which thiol bearing triazole moiety as the zinc binding functional group was introduced to a pyrazole based pharmacophore was synthesized and evaluated as potent and selective inhibitors of h-TNAP over h-NPP1. The biological screening against h-TNAP, h-IAP, h-NPP1 and h-NPP3 showed that many of the synthesized compounds are selective inhibitors of TNAP. Particularly, the compounds 10a-h, 10j, 10m-q, 10u, 10w and 10x displayed high potency and complete selectivity towards h-TNAP over h-NPP1. Compound 10q emerged as a highly potent inhibitor (IC50 = 0.16 μM or 160 nM) against h-TNAP with 127-fold increased inhibition compared to levamisole. On the other hand, compound 10e was found to be most selective inhibitor against the tested APs and NPPs (IC50 = 1.59 ± 0.36 μM). Binding sites architecture analysis, molecular-docking and molecular dynamics simulations (MDS), revealed the basis for h-TNAP and h-IAP ligand selectivity as well as selectivity towards h-TNAP over h-NPP1. These newly discovered inhibitors are believed to represent valuable lead structures to further streamline the generation of candidate compounds to target VC.
- Abida Ejaz, Syeda,Andleeb, Hina,Farman, Muhammad,Hameed, Shahid,Hussain, Muzammal,Iqbal, Jamshed,Sevigny, Jean,Yasinzai, Masoom,Zhang, Jiancun
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- Novel pyrazole-clubbed thiophene derivatives via Gewald synthesis as antibacterial and anti-inflammatory agents
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The aim of this study was to synthesize newer potent Schiff bases by condensing 2-amino-5-(2,4-dichlorophenyl)thiophene-3-carbonitrile and 1,3-disubstituted-1H-pyrazole-4-carbaldehydes, and to investigate their biological activity. The compounds were synthesized via Gewald synthesis and characterized by spectral data and elemental analyses. They were screened for their in vitro antibacterial and anti-inflammatory activities. The synthesized compounds were also evaluated for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv using the microplate Alamar Blue assay. Compounds 8b, 8c, 8f, 8g, 8k, 8n, and 8o showed promising antibacterial activity. The interactions between the substituted pyrazoles and bovine protein showed promising anti-inflammatory activity. The experimental results revealed compound 8a as a promising antitubercular agent. Hemolytic assays confirmed that the compounds are nontoxic, with percentage hemolysis ranging from 3.6 to 20.1, at a concentration of 1 mg/ml. The results suggest that the pyrazole ring and the substitution pattern on the heterocyclic moiety have an effect on the bioactivity.
- Nayak, Soukhyarani G.,Poojary, Boja,Kamat, Vinuta
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- Synthesis and Pharmacological Screening of Difluorophenyl Pyrazole Chalcone Conjugates as Antifungal, Anti-Inflammatory, and Antioxidant Agents
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Abstract: A new series of difluoro phenyl pyrazole chalcone was prepared by utilizing PEG 400 as a catalyst and investigated for their antifungal, anti-inflammatory, and antioxidant activity. The compounds 3-[3-(4-bromo-phenyl)-1-phenyl-1H-pyrazol-4-yl]-1-(2,4-difluloro-phenyl)-propenone (IVc), 1-(2,4-difluoro-phenyl)-3-[3-(4-methyl-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVd), 1-(2,4-difluoro-phenyl)-3-[3-(4-methoxy-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVe), and 1-(2,4-difluoro-phenyl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-propenone (IVg) exhibited promising antifungal activity at MIC of 25 and 50 μg/mL against selected human pathogenic fungi. Synthesized compounds 1-(2,4-difluoro-phenyl)-3-[3-(4-methoxy-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVe), 1-(2,4-difluoro-phenyl)-3-[3-(4-methyl-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVd), 1-(2,4-difluoro-phenyl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-propenone (IVg) and 1-(2,4-difluoro-phenyl)-3-[3-(4-fluoro-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVa) showed good anti-inflammatory activities comparable to the standard drug diclofenac sodium. Compounds 1-(2,4-difluoro-phenyl)-3-[3-(4-methoxy-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVe), 1-(2,4-difluoro-phenyl)-3-[3-(4-methyl-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVd) and 1-(2,4-difluoro-phenyl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-propenone (IVg) showed good hydrogen peroxide scavenging potential as compared to the butylated hydroxyl toluene. The conjugates 1-(2,4-difluoro-phenyl)-3-[3-(4-methoxy-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVe), 1-(2,4-difluoro-phenyl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-propenone (IVg), and 1-(2,4-difluoro-phenyl)-3-[3-(4-methyl-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVd) found more potent than standard ascorbic acid in DPPH radical scavenging assay as well as ferrous reducing power assay. The conjugates showed good interactions with the target protein in docking study.
- Bhosale, R. B.,Hublikar, M. G.,Jadhav, S. Y.,Kulkarni, A. A.,Peerzade, N. A.,Varpe, B. D.
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p. 1128 - 1135
(2020/12/30)
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- Microwave-Assisted Synthesis and Antimicrobial Activity of Novel Pyrazole–Indanone Hybrid Analogs
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Abstract: A simple and efficient microwave-assisted protocol has been developed for the synthetic of a series of novel pyrazole–indanone hybrid analogs. The target compounds have been synthesized by the Claisen–Schmidt condensation of different 1,3-diphenyl-1H-pyrazole-4-carbaldehydes with 2,3-dihydro-1H-inden-1-one in the presence of potassium hydroxide. The compounds were characterized by IR, 1H and 13C NMR, and mass spectra and were found to exhibit potent antimicrobial activity in vitro.
- Sundergoud, Sh.,Swamy, M. Kumara,Veerasomaiah, P.,Venkatesh, N.
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p. 1635 - 1639
(2020/10/22)
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- Pyrazolylphenanthroimidazole heterocycles: Synthesis, biological and molecular docking studies
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The synthesis of a series of novel pyrazolylphenanthroimidazoles 6a-6j has been accomplished utilizing a multi-step synthetic protocol, and characterized through physical and spectral techniques. Among them, the molecules possessing para-bromo (6d), para-methyl (6f) and para-nitro (6j) phenyl substituents on the pyrazole scaffold displayed similar anti-inflammatory activity and the one with no substituents on the aryl unit (6a) exhibited the highest anti-inflammatory profile. While investigating the DPPH radical scavenging activity, the synthesized chemical entity with a para-methoxyphenyl group attached at the pyrazole structural motif (6i) revealed the highest activity when compared to the other synthesized molecules. Furthermore, the evaluation of cytotoxic activity of the synthesized molecule (6a) exerted significant activity against both the pancreatic cell lines such as AsPC1 and SW1990. Besides, while performing the molecular docking studies of 6a with B-cell lymphoma 2, an appreciable binding affinity (-9.04 kcal mol-1) has been observed. The results of the present examination imply that these chemical entities could be used as efficient intermediates for the construction of biopertinent molecules. This journal is
- Sivaramakarthikeyan, Ramar,Iniyaval, Shunmugam,Lim, Wei-Meng,Hii, Ling-Wei,Mai, Chun-Wai,Ramalingan, Chennan
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p. 19612 - 19622
(2020/12/04)
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- Ultrasonic assisted synthesis of 2, 3-dihydroquinazolin-4(1H)-ones involving three-component reaction of isatoic anhydride, amines and pyrazole carbaldehydes catalyzed by [?-fe2o3?hap-So3H]
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The combination of [?-Fe2O3?HAp-SO3H] as a catalyst and ultrasonic effect catalyzed the synthesis of diverse derivatives of 2, 3-dihydroquinazolin-4(1H)-ones which is reported in this study. The products were synthesized via the one-pot three-component reaction of isatoic anhydride, amines and pyrazole carbaldehydes in water: EtOH catalyzed by recoverable [?-Fe2O3?HAp-SO3H]. This paper conducted an investigation of the effect of various solvents, temperatures and catalysts on the reactions. Short reaction times, mild reaction conditions, simple work-up, the desired yields and the use of an appropriate catalyst are the advantages of this novel method. The new derivatives were validated by using FT-IR,1HNMR, and13CNMR. Moreover, the synthesized compounds were screened for their an-timicrobial activity against bacterial strains.
- Mahmoodi, Nosrat O.,Moghadam, Kurosh R.,Nikpassand, Mohammad,Rasa, Mahdi,Sina, Kiana F.,Yahyazadeh, Asieh
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- Microwave-assisted synthesis and biological evaluation of pyrazole-4-carbonitriles as antimicrobial agents
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An efficient microwave-assisted method of synthesis of pyrazole-4-carbonitriles has been developed. Condensation of pyrazole-4-carbaldehydes with hydroxylamine hydrochloride followed by reaction of the resulting oximes with the Vilsmeier-Haack reagent pre-formed from phthaloyl dichloride and dimethylformamide under microwave irradiation afforded the corresponding pyrazole-4-carbonitriles in 73percent to 91percent yield. The operational simplicity, avoidance of toxic reagents such as POCl3, shorter reaction time, higher yield compared to the classical version, easy work up, and the use of the by-product in the regeneration of phthaloyl dichloride are the advantages of this methodology. All the target compounds were tested for antimicrobial activity against Gram-positive bacteria Bacillus cereus and Staphylococcus aureus; Gram-negative bacteria Escherichia coli and Yersinia enterocolitica, and the fungal species Candida albicans.
- Kumar, Anil,Kumari, Poonam,Singh, Karan,Sood, Sumit,Yadav, Ajar Nath
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- Microwave-assisted Vilsmeier-Haack synthesis of Pyrazole-4-carbaldehydes
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The synthesis of 4-formylpyrazoles using Vilsmeier-Haack reagent is a common protocol in pyrazole chemistry. An efficient microwave-assisted synthesis of 4-formylpyrazoles by employing Vilsmeier-Haack reagent (OPC-VH) derived from phthaloyl dichloride/dimethylformamide has been described. This method offers the advantages of operational simplicity, avoiding the use of POCl3 as toxic reagents and reuse of the by-product in the preparation of phthaloyl dichloride.
- Kumari, Poonam,Sood, Sumit,Kumar, Anil,Singh, Karan
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p. 796 - 804
(2019/11/28)
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- Synthesis and evaluation of novel benzotropolones as Atg4B inhibiting autophagy blockers
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Autophagy is an intracellular degradation/recycling pathway that provides nutrients and building blocks to cellular metabolism and keeps the cytoplasm clear of obsolete proteins and organelles. During recent years, dysregulated autophagy activity has been reported to be a characteristic of many different disease types, including cancer and neurodegenerative disorders. This has created a strong case for development of autophagy modulating compounds as potential treatments for these diseases. Inhibitors of autophagy have been proposed as a therapeutic intervention in, e.g., advanced cancer, and inhibiting the cysteine protease Atg4B has been put forward as a main strategy to block autophagy. We recently identified and demonstrated -both in vitro and in vivo - that compounds with a benzotropolone basic structure targeting Atg4B, can significantly slow down tumor growth and potentiate the effect of classical chemotherapy. In this study we report the synthesis and inhibition profile of new benzotropolone derivatives with additional structural modifications at 6 different positions. To obtain a solid inhibition profile, all compounds were evaluated on three levels, including two cell-based assays to confirm autophagy and intracellular Atg4B inhibition and an SDS-PAGE-based experiment to assess in vitro Atg4B affinity. Several molecules with a promising profile were identified.
- Tanc, Muhammet,Cleenewerck, Matthias,Kurdi, Ammar,Roelandt, Ria,Declercq, Wim,De Meyer, Guido,Augustyns, Koen,Martinet, Wim,Van der Veken, Pieter
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p. 163 - 168
(2019/03/19)
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- Imidazole-pyrazole hybrids: Synthesis, characterization and in-vitro bioevaluation against α-glucosidase enzyme with molecular docking studies
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Herein, substituted imidazole-pyrazole hybrids (2a-2n) were prepared via a multi component reaction employing pyrazole-4-carbaldehydes (1a-1d), ammonium acetate, benzil and arylamines as reactants. All the new compounds were characterized through their spectral and elemental analyses. Further these compounds were tested against α-glucosidase enzyme. The compounds 2k, 2l and 2n possessed good inhibition potencies, however, compounds 2f (IC50 value: 25.19 ± 0.004 μM) and 2m (IC50 value: 33.62 ± 0.03 μM) were the most effective compounds of the series. Furthermore, molecular docking helped to understand the binding interactions of 2f and 2m with the understudy yeast's α-glucosidase enzyme.
- Chaudhry, Faryal,Naureen, Sadia,Ashraf, Muhammad,Al-Rashida, Mariya,Jahan, Bakhat,Munawar, Munawar Ali,Khan, Misbahul Ain
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p. 267 - 273
(2018/11/10)
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- Synthesis of novel dihydrotriazine derivatives bearing 1,3-diaryl pyrazole moieties as potential antibacterial agents
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Three novel series of dihydrotriazine derivatives bearing 1,3-diaryl pyrazole moieties were designed, synthesized and evaluated in terms of their antibacterial and antifungal activities. Most of the synthesized compounds showed potent inhibition of several Gram-positive bacterial strains (including multidrug-resistant clinical isolates) and Gram-negative bacterial strains with minimum inhibitory concentration values in the range of 1–64 μg/mL. Compounds 4b and 4c presented the most potent inhibitory activity against Gram-positive bacteria (S. aureus 4220, MRSA 3167, QRSA 3519) and Gram-negative bacteria (E. coli 1924), with minimum inhibitory concentration values of 1 or 2 μg/mL. Compared with previous studies, these compounds exhibited a broad spectrum of inhibitory activity. The cytotoxic activity of the compounds 4a, 4b, 4c and 11n were assessed in L02 cells. In vitro enzyme study implied that compound 4c exerted its antibacterial activity through DHFR inhibition.
- Zhang, Tian-Yi,Zheng, Chang-Ji,Wu, Jie,Sun, Liang-Peng,Piao, Hu-Ri
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supporting information
p. 1079 - 1084
(2019/03/06)
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- Discovery of 1,3-diphenyl-1H-pyrazole derivatives containing rhodanine-3-alkanoic acid groups as potential PTP1B inhibitors
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Two series of 1,3-diphenyl-1H-pyrazole derivatives containing rhodanine-3-alkanoic acid groups were identified as competitive protein tyrosine phosphatase 1B (PTP1B) inhibitors. Among the compounds studied, IIIv was found to have the best in vitro inhibition activity against PTP1B (IC50 = 0.67 ± 0.09 μM) and the best selectivity (9-fold) between PTP1B and T-cell protein tyrosine phosphatase (TCPTP). Molecular docking studies demonstrated that compounds IIIm, IIIv and IVg could occupy simultaneously at both the catalytic site and the adjacent pTyr binding site. These results provide novel lead compounds for the design of inhibitors of PTP1B as well as other PTPs.
- Sun, Liangpeng,Wang, Peipei,Xu, Lili,Gao, Lixin,Li, Jia,Piao, Huri
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p. 1187 - 1193
(2019/03/26)
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- Synthesis of some hippuric acid substrate linked novel pyrazoles as antimicrobial agents
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Escalating resistance of microorganisms to the currently accessible antimicrobial drugs has forced to synthesize some novel biologically active compounds as efficient alternates via economical substrates. Hence, hippuric acid was used as one of the starting materials to synthesize pyrazole derivatives. All the synthesized compounds were characterized by IR, NMR (1H & 13C) and mass spectral data. The antimicrobial potential of synthesized compounds has been explored against four bacterial and two fungal strains. Among the 12 compounds, 3 compounds 8j, 8k and 8l were found to exhibit prominent antimicrobial potential as compared with the standards ciprofloxacin and amphotericin-B.
- Verma, Anil,Kumar, Vinod,Khare, Rajshree,Singh, Joginder
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p. 522 - 526
(2019/02/06)
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- Unveiling novel diphenyl-1H-pyrazole based acrylates tethered to 1,2,3-triazole as promising apoptosis inducing cytotoxic and anti-inflammatory agents
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Meagre and suboptimal therapeutic response along with the side effect profile associated with the existing anticancer therapy have necessitated the development of new therapeutic modalities to curb this disease. Bearing in mind the current scenario, a series of 1,2,3-triazole linked 3-(1,3-diphenyl-1H-pyrazol-4-yl)acrylates was synthesized following a multi-step reaction scheme. Initial screening for anticancer potential was done by in vitro sulforhodamine B assay against four human cancer cell lines- MCF-7 (breast), A549 (Lung) and HCT-116 and HT-29 (Colon). On evaluation, several compounds showed promising growth inhibition against all the cell lines, particularly compounds 6e, 6f and 6n. Among them, compound 6f displayed IC50 values of 1.962, 3.597, 1.764 and 4.496 μM against A549, HCT-116, MCF-7 and HT-29 cell lines respectively. Furthermore, the apoptosis inducing potential of the compounds was determined by Hoechst staining and DNA fragmentation assay. Colony formation inhibition assay was also carried out to determine the long term cytotoxic potential of the molecules. Moreover, compounds 6e, 6f and 6n were also evaluated for anti-inflammatory activity by protein albumin denaturation assay and red blood cell membrane stabilizing assay.
- Khan, Mohemmed Faraz,Anwer, Tarique,Bakht, Afroz,Verma, Garima,Akhtar, Wasim,Alam, M. Mumtaz,Rizvi, Moshahid Alam,Akhter, Mymoona,Shaquiquzzaman, Mohammad
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p. 667 - 678
(2019/04/05)
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- Probing the high potency of pyrazolyl pyrimidinetriones and thioxopyrimidinediones as selective and efficient non-nucleotide inhibitors of recombinant human ectonucleotidases
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With the aim to discover novel, efficient and selective inhibitors of human alkaline phosphatase and nucleotide pyrophosphatase enzymes, two new series of pyrazolyl pyrimidinetriones (PPTs) (6a–g) and thioxopyrimidinediones (PTPs) (6h–n) were synthesized in good chemical yields using Knoevenagel condensation reaction between pyrazole carbaldehydes (4a–g) and pharmacologically active N-alkylated pyrimidinetrione (5a) and thioxopyrimidinedione (5b). The inhibition potential of the synthesized hybrid compounds was evaluated against human alkaline phosphatase (h-TNAP and h-IAP) and ectonucleotidase (h-NPP1 and h-NPP3) enzymes. Most of the tested analogs were highly potent with a variable degree of inhibition depending on the functionalized hybrid structure. The detailed structure-activity relationship (SAR) of PPT and PTP derivatives suggested that the compound with unsubstituted phenyl ring from PPT series led to selective and potent inhibition (6a; IC50 = 0.33 ± 0.02 μM) of h-TNAP, whereas compound 6c selectively inhibited h-IAP isozyme with IC50 value of 0.86 ± 0.04 μM. Similarly, compounds 6b and 6h were identified as the lead scaffolds against h-NPP1 and h-NPP3, respectively. The probable binding modes for the most potent inhibitors were elucidated through molecular docking analysis. Structure-activity relationships, mechanism of action, cytotoxic effects and druglikeness properties are also discussed.
- Andleeb, Hina,Hameed, Shahid,Ejaz, Syeda Abida,Khan, Imtiaz,Zaib, Sumera,Lecka, Joanna,Sévigny, Jean,Iqbal, Jamshed
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- Design, synthesis, and biological evaluation of n-phenylpyrazole derivatives featuring nitrogen-containing side chains as potent antitumor agents
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ASERIES of novel N-phenylpyrazole containing acyl derivatives 3a, b, N-methylimidiazole 4, thiazole derivatives 6a-d, benzimidiazole derivatives 7a-c pyrane and pyridine 8, 9a, b, tetrazole 10, pyridodipyrimidine 11, and dihydronaphthaline derivatives 15 have been synthesized. The structure of the newly synthesized compounds was elucidated by IR, 1H NMR, 13C NMR, Mass spectra and Elemental analysis. The newly synthesized compounds were evaluated for their antitumor activity against three tumor cell lines, liver cancer (HepG2), human colonic carcinoma cell line (HCT-116), and human breast adenocarcinoma (MCF-7). Compounds 6d, 7b, c, 9b and 11 exhibited higher antitumor activity compared with the reference drug Doxorubicin.
- Hafez, Hend N.,El-Gazzar, Abdel-Rhman B.A.,Ali, Ahmed S.,Alakhras, Abbas I.A.
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p. 1493 - 1504
(2019/08/01)
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- Pyrazolo-benzothiazole hybrids: Synthesis, anticancer properties and evaluation of antiangiogenic activity using in vitro VEGFR-2 kinase and in vivo transgenic zebrafish model
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A series of new pyrazolo-benzothiazole hybrids (7–26) were synthesised and screened for their cytotoxic activity towards several cancer cell lines [colon (HT-29), prostate (PC-3), lung (A549), glioblastoma (U87MG)] and normal human embryonic kidney cell line (Hek-293T). Compounds 8, 9, 13, 14, 18, 19, 23, and 24 displayed significant activity, with compound 14 being particularly potent towards all the tested cancer cell lines with IC50 values in the range 3.17–6.77 μM, even better than reference drug axitinib (4.88–21.7 μM). Compound 14 also showed the strongest growth inhibition in 3D multicellular spheroids of PC-3 and U87MG cells. The mechanism of cellular toxicity in PC-3 cells was found to be cell cycle arrest and apoptosis induction through depolarisation of mitochondrial membrane potential, increased ROS production and subsequent DNA damage. Further, compound 14 displayed significant in vitro (VEGFR-2 inhibition) and in vivo [transgenic zebrafish Tg(flila:EGFP) model] antiangiogenic properties. Overall, these results provide strong evidence that compound 14 could be considered for a lead candidate in anticancer and antiangiogenic drug discovery.
- Reddy, Velma Ganga,Reddy, T. Srinivasa,Jadala, Chetna,Reddy, M. Soumya,Sultana, Faria,Akunuri, Ravikumar,Bhargava, Suresh K.,Wlodkowic, Donald,Srihari,Kamal, Ahmed
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- Synthesis and biological evaluation of thiazolidine-2,4-dione-pyrazole conjugates as antidiabetic, anti-inflammatory and antioxidant agents
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A series of fourteen novel thiazolidine-2,4-dione derivatives clubbed with pyrazole moiety were synthesized via four step reaction procedure. Reactions were monitored by thin layer chromatography and were characterized by physicochemical and spectrophotometric (IR, Mass, 1HNMR and 13CNMR) analysis. The spectral data were in good agreement with their structures. The title compounds were docked against peroxisome proliferated activated receptors (PPAR-γ) and alpha-amylase and further evaluated for in vivo and in vitro antidiabetic, in vitro anti-inflammatory and antioxidant activities. Compound GB14 exhibited significant blood glucose lowering activity and was also found to be active inhibitor of alpha-amylase. Compound GB7 was found to be potent anti-inflammatory agent in terms of reducing inflammatory markers (TNF-α, IL-β, MDA) and also showed antioxidant activity to good extent. Therefore, these compounds may be considered as promising candidates for the development of new antidiabetic agents.
- Bansal, Garima,Singh, Shamsher,Monga, Vikramdeep,Thanikachalam, Punniyakoti Veeraveedu,Chawla, Pooja
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- Novel acetohydrazide pyrazole derivatives: Design, synthesis, characterization and antimicrobial activity
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Eleven acetohydrazide linked pyrazole derivatives were designed and synthesized via condensation of acetohyadrazide with different substituted formyl pyrazole derivatives under mild reaction conditions. Synthesized compounds were characterized on the basis of IR, NMR (1H & 13C) and mass spectrometry. The antimicrobial activities of all the compounds were screened against four bacterial and two fungal strains. Among the synthesized compounds, three compounds viz. 6b, 6c and 6d were found as efficient antimicrobial agents in reference to the standard drugs viz. ciprofloxacin and amphotericin-B. Further, structure-activity relationship (SAR) study revealed that electron-withdrawing group enhances the antimicrobial potential of synthesized derivatives as compared to other groups present in the ring. Hence, among compounds 6b-c, compound 6d could be explored further against other microbes to prove its vitality.
- Verma, Anil,Kumar, Vinod,Kataria, Ramesh,Singh, Joginder
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p. 2740 - 2744
(2019/11/21)
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- Synthesis and antioxidant evaluation of dihydropyrimidinone integrated pyrazoles
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A series of novel ethyl 6-[2-(3-aryl-1-phenyl-1H-pyrazol-4-yl)vinyl]-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylates (9a-9d) has been synthesized by adopting a multistep synthetic strategy. The structure of the targets was confirmed on the basis of physical and spectral techniques. The synthetically achieved targets were evaluated for their antioxidant activity by in-vitro DPPH free radical scavenging assay. Of the chemical entities screened, most of them exhibit good to better radical scavenging profile and among those, the nitro substituent bearing molecule 9c displayed the highest activity (82%) with IC50 value 621.6 μM. Further, as a representative molecule, compound 9a has been subjected to density functional theory calculations employing B3LYP method with 6311(++G) basis set to optimize its structure.
- Padmavathy, Krishnaraj,Sutha, Peramasivan,Krishnan, Kannan G.,Kumar, Chandran U.,Iniyaval, Shun-Mugam,Ramalingan, Chennan
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p. 969 - 977
(2019/11/22)
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- Pyrazole-4-carboxylic Acids from Vanadium-catalyzed Chemical Transformation of Pyrazole-4-carbaldehydes
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The conversion of aldehydes into carboxylic acids using oxidizing agents is a common protocol in transformation chemistry. An efficient oxidation strategy of transformation of pyrazole-4-aldehydes to the corresponding acids using vanadium catalysts in the presence of 30% H2O2 as an oxidant is described. The catalytic technology was successfully applied to a range of various 4-formylpyrazoles, and plausible mechanism is also discussed.
- Bala, Renu,Kumari, Poonam,Sood, Sumit,Phougat, Harshita,Kumar, Anil,Singh, Karan
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p. 1787 - 1793
(2019/04/30)
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- Selective synthesis of functionalized pyrazoles from 5-amino-1H-pyrazole-4-carbaldehydes with sodium nitrite: 5-Amino-4-nitrosopyrazoles and pyrazole-4-carbaldehydes
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A novel and efficient redox reaction was developed to react 5-amino-1H-pyrazole-4-carbaldehyde with sodium nitrite (NaNO2) in an acidic solution (HCl/MeOH) to generate 5-amino-4-nitrosopyrazole, pyrazole-4-carbaldehyde, or diazenylpyrazole selectively. The results showed that 5-amino-4-nitrosopyrazoles were formed as the major product in the diluted acidic solution (≤2 N HCl in MeOH solution) through redox, formylation, and nitrosation reactions of NaNO2. Intriguingly, pyrazole-4-carbaldehyde was the main product under 6 N HCl in MeOH solution.
- Hsiao, Rong-Hong,Tseng, Ching-Chun,Xie, Jia-Jun,Tsai, Shuo-En,Uramaru,Lin, Ching-Ya,Chern, Ching-Yuh,Wong, Fung Fuh
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supporting information
p. 4561 - 4569
(2019/07/10)
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- Solubility and solution thermodynamics of novel pyrazolo chalcone derivatives in various solvents from 298.15?K to 328.15?K
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Some novel pyrazolo chalcone derivatives have been synthesized and characterization of these synthesized compounds was done by IR, 1H NMR, 13C NMR and mass analysis. The solubility of pyrazolo chalcone derivatives in methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, ethyl acetate and acetonitrile was measured by gravimetric method over a temperature range (298.15 to 328.15) K at atmospheric pressure. The solubility of synthesized compounds is found to increase linearly with temperature. Further, in alcoholic solvents, solubility is maximum in 1-pentanol and minimum in methanol whereas in non-alcoholic solvents, solubility is greater in ethyl acetate and minimum in acetonitrile. The experimental solubility data were correlated with temperature by modified Apelblat and Buchowski-Ksiazczak λh equations. The experimental data and model parameters would be useful for optimizing the process of purification. Some thermodynamic parameters such as dissolution enthalpy, Gibb's free energy and entropy of mixing have also been calculated by Van't Hoff analysis. Further, excess enthalpy of solutions has been calculated using Buchowski-Ksiazczak λh equation.
- Baluja, Shipra,Hirapara, Asmita
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p. 692 - 704
(2019/01/10)
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- Method for synthesizing ellagic acid from gallic acid derivative
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The invention discloses a method for synthesizing ellagic acid from a gallic acid derivative. The method comprises the technical steps: utilizing the gallic acid derivative and 10 to 25% NH3.H2O for being ammonized in a 45 to 55 DEG C water bath pot for 5 to 24h; then adding an oxidizing agent into an ammonizing solution to perform oxidizing reaction for 5 to 24h; after reaction finishes, filtering filtrate and dissolving filter cake by a NaOH water solution; extracting an alkali solution by an organic solvent; then utilizing a HCl solution to adjust a water-phase pH to 1.0 to 2.5; crystallizing and filtering; vacuum drying to obtain light yellow ellagic acid. According to the method, the raw materials are cheap, a reaction temperature is moderate, and a reaction process is safe and easy to control; a yield of the method is higher than reported yields and can reach 70% or above; the color of the ellagic acid synthesized by the method is light yellow, and the purity of the ellagic acidcan reach 98% or above.
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Paragraph 0018; 0019
(2018/09/08)
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- Synthesis, Characterization, Molecular Docking Studies and Anticancer Activity of Schiff Bases Derived from 3-(Substituted phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde and 2-Aminophenol
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Abstract: A series of new Schiff bases were synthesized by microwave assisted reactions of substituted 1-phenyl-1H-pyrazole-4-carbaldehyde and 2-aminophenol in ethanol and characterized by elemental analysis and spectroscopic (IR, 1H NMR and MS) data. The crystal structures of four compounds were studied using single-crystal XRD data. Molecular docking studies of all synthesized compounds were performed into the binding site of a protein 3GCW to gain comprehensive understanding into possible binding modes. These compounds were also screened for anticancer activity against the liver (HEP-G2) cell line using the sulphorhodamine-B assay method. Adriamycin i.e. doxorubicin was used as reference standard. One of the compounds shows anticancer activity close to the famous anticancer agent doxorubicin, which was used as control in this study. It is observed that all molecules show activity close to the standard in high concentrations only. Graphical Abstract: Present study describes the anticancer activity and crystal structure study of Schiff bases of substituted pyrazole-4-carbaldehyde with 2-aminophenol. Docking study of all compounds against human hepatoma cell line, HEP-G2 correlates with in vitro activity. [Figure not available: see fulltext.].
- Wazalwar, Sachin S.,Banpurkar, Anita R.,Perdih, Franc
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p. 185 - 199
(2018/08/27)
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- Design, synthesis and cytotoxicity evaluation of pyrazolyl pyrazoline and pyrazolyl aminopyrimidine derivatives as potential anticancer agents
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In an attempt to find bio-active heterocyclic analogues, a series of novel 1-(5-(3-(aryl)-1-phenyl-1H-pyrazol-4-yl)-3-(pyridin-3-yl)-4,5-dihydropyrazol-1-yl)ethanones 5a–i and 4-(3-(aryl)-1-phenyl-1H-pyrazol-4-yl)-6-(pyridine-3-yl)pyrimidin-2-amines 6a–i were designed, synthesized, and evaluated for their in vitro cytotoxicity against a panel of human cancer cell lines namely, HeLa (human cervix), NCI-H460 (human lung), PC-3 (human prostate), and NIH-3T3 (mouse embryo fibroblasts) cell lines. Most of these compounds exhibited moderate to good cytotoxicity against the tested cancer cell lines and weak toxicity against normal cell line. Analogs 5f, 5g, 5i, 6b–g showed significant cytotoxicity as compared to the standard drug etoposide. The compound 6g exhibited superior activity with IC50 value of 5.47 ± 0.44 μM against Hela cancer cell line.
- Alam, Raquib,Alam, Aftab,Panda, Amulya K.,Rahisuddin
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p. 560 - 570
(2017/10/13)
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- Synthesis and antimicrobial evaluation of some heterocyclic compounds from 3-Aryl-1-phenyl-1H-pyrazole-4-carbaldehydes
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A new series of chalcones, pyrazolinyl-pyrazoles, pyrazole-4-carbaldehyde oximes, pyrazole-4-carbonitriles, 5-pyrazolyl-1,2,4-Triazolidine-3-Thiones, and Knoevenagel condensation products was synthesized from 3-Aryl-1-phenyl-1H-pyrazole-4-carbaldehydes. Most reactions were carried out either without solvent or in the presence of water as a green solvent. The structure of synthesized compounds was characterized by spectral and elemental analysis. The synthesized compounds were tested in vitro for their antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Candida albicans in comparison with imipenem (intravenous β-lactam antibiotic) and clotrimazole (antifungal medication) as reference drugs by using the agar diffusion technique. 3-Aryl-1-phenyl-1H-pyrazole-4-carbonitriles 8b, 8c, and 8d showed significant antifungal activity against the fungus C. albicans.
- Ramadan, El Sayed,Sharshira, Essam M.,El Sokkary, Ramadan I.,Morsy, Noussa
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p. 389 - 397
(2018/05/30)
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- Thiazolo[3,2-a] Pyrimidones as a Novel Anti-TB Agents
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A series of novel thiazolo pyrimidine derivatives were designed, synthesized, and assessed for their in vitro anti-mycobacterial activities. All hybrids displayed considerable antitubercular activities against primary Mycobacterium smegmatis mc2 155 screening and successive Mycobacterium tuberculosis H37Rv. In particular, the hybrid entities 13 and 14 (minimum inhibitory concentration: 47 and 39?μg/mL) were found to be equipotent candidates with first-line antitubercular agent rifampicin, which could act as a lead for further optimization.
- Jadhav, Sunil B.,Fatema, Samreen,Bhagat, Sunil S.,Farooqui, Mazahar
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p. 2893 - 2900
(2018/10/24)
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- HALOGENATED BENZOTROPOLONES AS ATG4B INHIBITORS
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The present invention relates to compounds having a benzotropolone core, and compositions containing said compounds acting as ATG4B inhibitors, thereby inhibiting autophagy. Moreover, the present invention provides processes for the preparation of the disclosed compounds, as well as methods of using them, for instance as a medicine, in particular for the treatment of cell proliferative disorders, such as cancer.
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- One pot synthesis of thiazolo[2,3-b]dihydropyrimidinone possessing pyrazole moiety and evaluation of their anti-inflammatory and antimicrobial activities
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A series of pyrazole integrated thiazolo[2,3-b]dihydropyrimidinone derivatives were synthesized as dual anti-inflammatory and antimicrobial agents. Among the compounds studied, 3-fluoro-4-methylphenyl analogues (3a, 3e, and 3i) are considered to be promising leads for novel anti-inflammatory agents compared with the standard drug. The superior antimicrobial property of the compounds 3a, 3b, and 3d indicates that 3-(3,4-dichlorophenyl)-1-phenyl-1H-pyrazole substitution is a favourable site for high activity. Molecular docking studies were carried out in order to predict the hypothetical binding mode of these compounds to the COX-2 isoenzyme. The results of the present study suggest that 1,3-diaryl pyrazole substitution on thiazolo[2,3-b]dihydropyrimidinone derivatives might potentially constitute a novel class of anti-inflammatory agents with antimicrobial property and could be an interesting approach for the design of new selective COX-2 inhibitory agents.
- Viveka, Shivapura,Dinesha,Nagaraja, Gundibasappa Karikannar,Shama, Prasanna,Basavarajaswamy, Guru,Rao, K. Poornachandra,Yanjarappa Sreenivasa, Marikunte
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p. 171 - 185
(2018/04/17)
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- Pyrazole-pyrazoline as promising novel antimalarial agents: A mechanistic study
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A series of pyrazole-pyrazoline substituted with benzenesulfonamide were synthesized and evaluated for their antimalarial activity in vitro and in vivo. The compounds were active against both chloroquine (CQ) sensitive (3D7) and CQ resistant (RKL-9) strains of Plasmodium falciparum. Seven compounds (7e, 7i, 7j, 7l, 7m, 7o and 7p) exhibiting EC50 less than 2 μM. A mechanistic study of compound 7o revealed that these compound act through the inhibition of β-hematin. The study indicated that these compounds can serve as lead compounds for further development of potent antimalarial drugs.
- Kumar, Gautam,Tanwar, Omprakash,Kumar, Jitender,Akhter, Mymoona,Sharma, Supriya,Pillai,Alam, Md Mumtaz,Zama
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p. 139 - 147
(2018/03/09)
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- Aqueous phase synthesis, crystal structure and biological study of isoxazole extensions of pyrazole-4-carbaldehyde derivatives
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A series of novel isoxazol derivatives was synthesized by green route in aqueous phase at room temperature by the reaction of 3-methyl-4H-isoxazol-5-one with 3-(substituted phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde by one-pot Knoevenagel condensation method using sodium benzoate as a catalyst. Compounds were characterized on the basis of IR, 1H NMR, mass spectroscopy and melting point determination. Crystal structures of five compounds were determined by X-ray diffraction. The compounds formed were screened for antibacterial and antifungal activity. Some compounds showed activity close to ampicillin against E. coli, S. aureus, and S. pyogenus. Two compounds showed antifungal activity against C. albicans close to standard greseofulvin.
- Wazalwar, Sachin S.,Banpurkar, Anita R.,Perdih, Franc
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p. 258 - 267
(2017/09/08)
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- Synthesis of novel α,α-difluoro-β-hydroxycarbonyl pyrazole derivatives as antioxidant, anti-inflammatory and anticancer agents
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A series of novel α,α-difluoro-β-hydroxyl pyrazole esters was prepared by Reformatsky reaction. Subsequently, these esters were converted to acids and hydrazides. All the synthesized compounds were evaluated for their in vitro antioxidant, anti-inflammatory and anticancer potential at various concentrations (50, 100 μM). Compounds 4d and 6e were found to be potent (93.19 and 90.91 %) and compounds 5d, 6c and 5f were good OH radical scavengers (79.55–72.73 %) as compared to the standard drug ascorbic acid (88.63 %). Compounds 6a, 5c, 6f, 4d and 5a showed significant 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity (75.95–70.89 %). All the compounds have shown higher cyclooxygenase-1 (COX-1) inhibition over cyclooxygenase-2 (COX-2) at concentrations 100 and 50 μM. Compounds 5f, 6b, 4a, 5c, 4f, 5 and 6d showed significant COX-2 inhibition (38.56–28.30 %) at a concentration of 100 μM compared to standard drug aspirin (11.11 %). Compounds 6f, 6e and 5f have shown significant cytotoxicity against MCF-7 (51.03–40.59 %), whereas 6d, 5f and 5a showed moderate cytotoxicity against HL-60 (26.98–20.21 %) cancer cell lines compared to the methotrexate as reference standard (68.42 and 54.29 % respectively). All compounds have shown almost neglisible cytotoxicity against normal cell line 293.
- Mukarram, Salman,Bandgar, Babasaheb P.,Shaikh, Rafik U.,Ganapure, Shriram D.,Chavan, Hemant V.
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p. 262 - 273
(2017/01/12)
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- Design, Synthesis, and Cytotoxicity Evaluation of 3-(5-(3-(aryl)-1-phenyl-1H-pyrazol-4-yl)-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)pyridine and 5-(3-(aryl)-1-phenyl-1H-pyrazol-4-yl)-3-(pyridin-3-yl)-4,5-dihydropyrazole-1-carbaldehyde Derivatives as Potential Anticancer Agents
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In an attempt to find bio-active small molecules, a series of novel 3-(5-(3-(aryl)-1-phenyl-1H-pyrazol-4-yl)-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)pyridine 5a–i and 5-(3-(aryl)-1-phenyl-1H-pyrazol-4-yl)-3-(pyridin-3-yl)-4,5-dihydropyrazole-1-carbaldehyde 6a–i were designed, synthesized, and evaluated for their in vitro cytotoxic activity against a panel of human cancer cell lines namely; HeLa (human cervix), NCI-H460 (human lung), PC-3 (human prostate), and NIH-3T3 (mouse embryo fibroblasts) normal cell line. Most of these compounds exhibited moderate to good cytotoxic activity against the tested cancer cell lines and weak toxicity against normal cell line. Analogues 5b, 5f, 5g, 6b, and 6g showed significant cytotoxicity as compared to standard drug etoposide. Among all the synthesized compounds, compound 6g displayed superior cytotoxicity with an IC50 value of 7.98 ± 1.08 μM for Hela cancer cell line.
- Alam, Raquib,Alam, Md. Aftab,Panda, Amulya K.,Rahisuddin
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p. 1812 - 1821
(2017/05/29)
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- Sulfamic acid as a green, reusable catalyst for stepwise, tandem & one-pot solvent-free synthesis of pyrazole derivatives
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Sulfamic acid (SA) is a bi-functional, cost-effective and reusable green catalyst for the synthesis of 4-(pyrazol-4-yl)methylenepyrazol-5(4H)-one derivatives by one-pot, three-component condensation of pyrazol-4-carbaxaldehydes, β-ketoesters and phenyl hydrazine (Route-I). In addition to this method, another simple condensation of pyrazol-4-carbaxaldehydes with pyrazolone in the presence of SA under the solvent-free condition in good yield is reported. The merits of these protocols are mild conditions, non-aqueous workup, high yields, easy availability of the catalyst, no chromatographic separation and inexpensive solid acid catalyst. Furthermore, SA could be recycled and reused for five times without losing its catalytic activity.
- Konkala, Veera Swamy,Dubey, Pramod Kumar
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p. 1571 - 1576
(2017/07/17)
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- Design, synthesis, biological evaluation and molecular modelling studies of novel diaryl substituted pyrazolyl thiazolidinediones as potent pancreatic lipase inhibitors
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A series of novel diaryl substituted pyrazolyl 2,4-thiazolidinediones were synthesized via reaction of appropriate pyrazolecarboxaldehydes with 2,4-thiazolidinedione (TZD) and nitrobenzyl substituted 2,4-thiazolidinedione. The resulting compounds were screened in vitro for pancreatic lipase (PL) inhibitory activity. Two assay protocols were performed viz., methods A and B using p-nitrophenyl butyrate and tributyrin as substrates, respectively. Compound 11e exhibited potent PL inhibitory activity (IC50?=?4.81?μM and Xi50?=?10.01, respectively in method A and B), comparable to that of the standard drug, orlistat (IC50?=?0.99?μM and Xi50?=?3.72). Presence of nitrobenzyl group at N-3 position of TZD and nature of substituent at para position of phenyl ring at C-3 position of pyrazole ring notably affected the PL inhibitory activity of the tested compounds. Enzyme inhibition kinetics of 11e revealed its reversible competitive inhibition, similar to that of orlistat. Molecular docking studies validated the rationale of pharmacophoric design and are in accordance to the in vitro results. Compound 11e exhibited a potential MolDock score of ?153.349?kcal/mol. Further, the diaryl pyrazolyl wing exhibited hydrophobic interactions with the amino acids of the hydrophobic lid domain. Moreover, the carbonyl group at 2nd position of the TZD ring existed adjacent to Ser 152 (≈3??) similar to that of orlistat. A 10?ns molecular dynamics simulation of 11e–PL complex revealed a stable binding conformation of 11e in the active site of PL (Maximum RMSD?≈?3??). The present study identified novel thiazolidinedione based leads with promising PL inhibitory activity. Further development of the leads might result in potent PL inhibitors.
- S.N.C., Sridhar,Bhurta, Deendyal,Kantiwal, Dharmvir,George, Ginson,Monga, Vikramdeep,Paul, Atish T.
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supporting information
p. 3749 - 3754
(2017/07/27)
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