- Bis(4,5-dihydropyrazole) derivatives: Synthesis, characterization and antimicrobial-antioxidant evaluations
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In the present work, five new bispyrazolines 3(a-e) have been prepared from the cyclization reaction of bischalcones 2(a-e) with phenyl hydrazine under alcoholic medium. The bischalcones 2(a-e) were synthesized by using the alkylation of chalcone 1 with a
- Yusuf, Mohamad,Thakur, Saloni
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- Efficient synthesis of small molecule macroarrays: optimization of the macroarray synthesis platform and examination of microwave and conventional heating methods
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We report a method for the efficient construction of small molecule macroarrays using microwave-assisted SPOT-synthesis. Macroarrays of 1,3-diphenylpropenones (chalcones) were synthesized rapidly and in high purity starting from robust, Wang-linker-deriva
- Bowman, Matthew D.,Jacobson, Megan M.,Pujanauski, Brian G.,Blackwell, Helen E.
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- Aldoxime- and hydroxy-functionalized chalcones as highly potent and selective monoamine oxidase-B inhibitors
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A panel of 30 chalcone derivatives, including 19 aldoxime-chalcone ethers (ACE), and 11 hydroxyl?chalcones (HC), previously synthesized using a Pd-catalyzed C–O cross-coupling method were evaluated for their inhibitory activities against monoamine oxidases (MAOs), cholinesterases (ChEs), and β-secretase (BACE-1). HC6 was the most potent inhibitor of MAO-B with an IC50 value of 0.0046 μM and a selectivity index (SI) of 1,113. HC3 also potently inhibited MAO-B (IC50 = 0.0067 μM) and had the highest SI (1,455). ACE7 and ACE15 were also potent MAO-B inhibitors (IC50 = 0.012 and 0.018 μM, respectively), with SIs of 260 and 1,161, respectively. HC3 and HC6 were reversible competitive inhibitors of MAO-B, with Ki values of 0.0036 and 0.0013 μM, respectively. A structure–activity relationship revealed that methyl and fluorine substituents contributed to increasing both inhibition and selectivity. ACE7 was the most effective inhibitor of MAO-A (IC50 = 1.49 μM), followed by ACE3 (IC50 = 3.75 μM). No compounds effectively inhibited AChE, BChE, or BACE-1. A docking simulation showed that the ligand efficiency and docking scores of HC3 and HC6 toward MAO-B were consistent with the experimental IC50 values. These results suggest that HC3 and HC6 can be considered promising candidates for the treatment of neurological disorders.
- Oh, Jong Min,Rangarajan,Chaudhary, Reeta,Gambacorta, Nicola,Nicolotti, Orazio,Kumar, Sunil,Mathew, Bijo,Kim, Hoon
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- From Celecoxib to a Novel Class of Phosphodiesterase 5 Inhibitors: Trisubstituted Pyrazolines as Novel Phosphodiesterase 5 Inhibitors with Extremely High Potency and Phosphodiesterase Isozyme Selectivity
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A ligand-based approach involving systematic modifications of a trisubstituted pyrazoline scaffold derived from the COX2 inhibitor, celecoxib, was used to develop novel PDE5 inhibitors. Novel pyrazolines were identified with potent PDE5 inhibitory activit
- Abdel-Halim, Mohammad,Sigler, Sara,Racheed, Nora A. S.,Hefnawy, Amr,Fathalla, Reem K.,Hammam, Mennatallah A.,Maher, Ahmed,Maxuitenko, Yulia,Keeton, Adam B.,Hartmann, Rolf W.,Engel, Matthias,Piazza, Gary A.,Abadi, Ashraf H.
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supporting information
p. 4462 - 4477
(2021/05/04)
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- Chalcone-Supported Cardiac Mesoderm Induction in Human Pluripotent Stem Cells for Heart Muscle Engineering
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Human pluripotent stem cells (hPSCs) hold great promise for applications in cell therapy and drug screening in the cardiovascular field. Bone morphogenetic protein 4 (BMP4) is key for early cardiac mesoderm induction in hPSC and subsequent cardiomyocyte derivation. Small-molecular BMP4 mimetics may help to standardize cardiomyocyte derivation from hPSCs. Based on observations that chalcones can stimulate BMP4 signaling pathways, we hypothesized their utility in cardiac mesoderm induction. To test this, we set up a two-tiered screening strategy, (1) for directed differentiation of hPSCs with commercially available chalcones (4’-hydroxychalcone [4’HC] and Isoliquiritigen) and 24 newly synthesized chalcone derivatives, and (2) a functional screen to assess the propensity of the obtained cardiomyocytes to self-organize into contractile engineered human myocardium (EHM). We identified 4’HC, 4-fluoro-4’-methoxychalcone, and 4-fluoro-4’-hydroxychalcone as similarly effective in cardiac mesoderm induction, but only 4’HC as an effective replacement for BMP4 in the derivation of contractile EHM-forming cardiomyocytes.
- Raad, Farah S.,Khan, Taukeer A.,Esser, Tilman U.,Hudson, James E.,Seth, Bhakti Irene,Fujita, Buntaro,Gandamala, Ravi,Tietze, Lutz F.,Zimmermann, Wolfram
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supporting information
p. 3300 - 3305
(2021/09/02)
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- New class of hybrids based on chalcone and melatonin: a promising therapeutic option for the treatment of colorectal cancer
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Considering that conventional chemotherapy provides only a limited increase of overall survival for patients with colorectal cancer (CRC), and resistance is a major cause of therapeutic failure, the emergence of new therapies is needed. Development of dif
- Arias, Juan D.,Cardona-G, Wilson,Herrera-R, Angie,Moreno, Gustavo,Yepes, Andrés F.
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p. 2240 - 2255
(2021/10/20)
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- Development of pH-activatable fluorescent probes for rapid visualization of metastatic tumours and fluorescence-guided surgeryviatopical spraying
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A series of pH-activatable aza-BODIPY-based fluorescent probes were developed for rapid cancer visualization and real-time fluorescence-guided surgery by harnessing topical spraying. These probes exhibited good water-solubility, a tunable pKafrom 5.0 to 7.9, and stable intense NIR emission at ~725 nm under acidic conditions.AzaB5with a pKavalue of 6.7 was able to rapidly and clearly visualize pulmonary and abdominal metastatic tumours including tiny metastases less than 2 mmviatopical spraying, further improving intraoperative fluorescence-guided resection. We believe thatAzaB5is promising as a powerful tool to rapidly delineate a broad range of malignancies and assist surgical tumour resection.
- Cao, Wenwen,Li, Xiaoxin,Wu, Peng,Xiong, Hu
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p. 10636 - 10639
(2021/10/19)
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- Discovery of CAPE derivatives as dual EGFR and CSK inhibitors with anticancer activity in a murine model of hepatocellular carcinoma
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Caffeic acid phenethyl ester (CAPE), a bioactive component extracted from propolis of honeybee hives, can inhibit hepatocellular carcinoma (HCC). In order to explore more stable CAPE derivatives, 25 compounds were designed, synthesized, and pharmacologically assessed in vitro and in vivo as anti-tumor agents in HCC. Compounds 8d, 8f, 8l, 8j, and 8k showed favorable antiproliferative activity than other compounds including CAPE in the HCC cell lines. Based on the result of QTRP (Quantitative Thiol Reactivity Profiling), epidermal growth factor receptor (EGFR) and C-terminal Src kinase (CSK) were supposed to the targets of 8f, which was confirmed by binding mode analysis. Furthermore, compounds 8f, 8l, 8j, 8k, 8g, and 8h showed potent inhibitory effects against both CSK and EGFR than other derivatives in an ADP-Glo kinase assay. The representative compound, 8f, potently inhibited various tumor growth in murine model including murine hepatocellular carcinoma H22, meanwhile downregulating the EGFR/AKT pathway and enhancing T cell proliferation through inhibition of CSK. Metabolic stability in vitro suggested 8f and 8k were more stable in mouse plasma than CAPE and susceptible to metabolism in liver microsomes. The overall excellent profile of compound 8f makes it a potential candidate for further preclinical investigation.
- Liu, Xiaoyu,Du, Qianqian,Tian, Caiping,Tang, Mei,Jiang, Yingjun,Wang, Yong,Cao, Yang,Wang, Zhe,Wang, Zhenwei,Yang, Jing,Li, Yan,Jiao, Xiaozhen,Xie, Ping
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- Design, Synthesis, and Antimicrobial Evaluation of Novel [1,2,4]Triazolo[3,4-b][1,3,4]thiadiazepine Derivatives
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Abstract: The title compounds,3,3′,3″,3′′′-[methylenebis(oxybenzene-5,1,3-triyl)]tetrakis(6,8-diaryl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepines), were synthesized startingfrom dimethyl 4-hydroxyisophthalate which was reacted with dibromomethane toobtain tetramethyl 5,5′-[methylenebis(oxy)]di(benzene-1,3-dicarboxylate). Thelatter was treated with excess hydrazine hydrate, and the resultingtetrahydrazide was converted to tetrakis-1,2,4-triazolyl derivative viacyclization with ethanolic potassium hydroxide, carbon disulfide, and hydrazinehydrate. In the final stage, cyclocondensation with substituted chalconesafforded the target products. The structure of the newly synthesized compoundswas confirmed by elemental analyses and FT-IR and NMR spectra, and theirantimicrobial activities against some bacterial and fungal strains wereestimated by the disc diffusion method.
- Ayyash
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p. 2165 - 2170
(2021/02/09)
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- Silica-supported heterogeneous catalysts-mediated synthesis of chalcones as potent urease inhibitors: in vitro and molecular docking studies
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Abstract: We herein report a facile and high yielding protocol for silica-supported heterogeneous catalysts-mediated synthesis of chalcones. A comparison of results of our synthesis with conventional synthetic protocols is also being offered to assess the efficiency of the prepared catalysts. Biological evaluation of the newly synthesized compounds as urease inhibitors was performed. Most of the compounds were found to have potent urease inhibition activity. The chalcone 3-(3-hydroxyphenyl)-1-phenylpropenone was found to be the most potent with percentage inhibition 86.17 ± 0.89 and half maximal inhibitory concentration (IC50) value 11.51 ± 0.03 μM. The molecular docking study emphasized that the same congeners 3-(furan-2-yl)-1-(4-hydroxyphenyl)propenone, 3-(4-hydroxyphenyl)-1-(4-methoxyphenyl)propanone, and 3-[4-(dimethylamino)phenyl]-1-(p-tolyl)propenone showed very good inhibitory potential against urease and show a higher docking scores 5718, 5940, 5596 and an ACE of ? 246.66, ? 244.79, and ? 243.06 kJ/mol, respectively than the control ligand. Graphic abstract: [Figure not available: see fulltext.].
- Sultan, Aeysha,Shajahan, Shanavas,Ahamad, Tansir,Alshehri, Saad M.,Sajjad, Noreen,Mehr-un-Nisa,Rehman, Mian Habib Ur,Torun, Lokman,Khalid, Muhammad,Acevedo, Roberto
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p. 123 - 133
(2020/01/11)
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- New chalcone derivatives: Synthesis, antiviral activity and mechanism of action
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In this work, twenty-eight chalcone derivatives containing a purine (sulfur) ether moiety were synthesized and their antiviral activities were evaluated. Biological results showed that compound 5d exhibited outstanding inactive activity against tobacco mosaic virus (TMV) in vivo (EC50 = 65.8 μg mL-1), which is significantly superior to that of ribavirin (EC50 = 154.3 μg mL-1). Transmission electron microscopy indicated that compound 5d can break the integrity of TMV particles. The results of microscale thermophoresis, fluorescence titration and molecular docking showed that compound 5d had stronger combining affinity (Ka = 1.02 ×105 L mol-1, Kd = 13.4 μmol L-1) with TMV coat protein (TMV-CP), which is due to the formation of five hydrogen bonds between compound 5d and the amino-acid residues of TMV-CP. These findings revealed that compound 5d can effectively inhibit the infective ability of TMV. This work provides inspiration and reference for the discovery of new antiviral agents.
- Fu, Yun,Gan, Xiuhai,Hu, Deyu,Liu, Dan,Ren, Xiaoli,Song, Baoan,Zeng, Huanan
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p. 24483 - 24490
(2020/07/15)
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- Aminoalkylated phenolic chalcones: Investigation of biological effects on acetylcholinesterase and carbonic anhydrase I and II as potential lead enzyme inhibitors
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Background: Phenolic Mannich bases have been reported as acetylcholinesterase (AChE) inhibitors for the medication of Alzheimer's disease. Carbonic Anhydrases (CAs) are molecular targets for anticonvulsant, diuretic and antiglaucoma drugs in the clinic. P
- Yamali, Cem,Gul, Halise Inci,Cakir, Tahir,Demir, Yeliz,Gulcin, Ilhami
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p. 1283 - 1292
(2020/10/06)
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- Efficient solvent- And temperature-tuned access to aldoxime ethers and phenolic functions by Pd-catalyzed C-O cross-coupling of aldoximes with aryl bromides and bromo-chalcones
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A single method with a functionality switching option was developed for the first time for the Pd-catalyzed C-O cross-coupling of aryl bromides and bromo-chalcones with aldoximes. The ligand tBuXPhos (L2) was found to be an effective supporting ligand for the Pd-catalyzed coupling of aldoximes with bromo coupling partners. The functionality switching from oxime ethers to a phenolic or hydroxy group was driven by solvent or temperature. This method offers the products in good to excellent yields in short reaction times.
- Reeta,Rangarajan,Kaushik, Kumar,Singh, Rishi Pal,Singh, Manjula,Singh, Raj Pal
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supporting information
p. 1326 - 1336
(2020/02/11)
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- Synthesis and Pharmacological Evaluation of 4-Aryloxyquinazoline Derivatives as Potential Cytotoxic Agents
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In the present study, novel 4-aryloxyquinazoline derivatives were synthesized and screened for in vitro cytotoxicity on human cancer cell lines at 10 μM. Some of the synthesized compounds displayed moderate to significant and selective cytotoxic activity
- Malhotra, Anjleena,Kaur, Tejinder,Bansal, Ranju
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p. 2902 - 2911
(2019/08/26)
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- Synthesis, in vitro antigiardial activity, SAR analysis and docking study of substituted chalcones
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A series of 15 chalcones-bearing substituents at positions 2, 4, and 5 of rings A and B were synthesized using microwave-assisted Claissen–Smichdt condensation and evaluated for their activity against Giardia lamblia and Green monkey kidney cells. Five co
- Cáceres-Castillo, David,Carballo, Rubén M.,Graniel-Sabido, Manlio,Mena-Rejón, Gonzalo J.,Mirón-López, Gumersindo,Moo-Puc, Rosa E.,Quijano-Qui?ones, Ramiro
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- Synthesis, Structure, and Anti-Inflammatory Activity of Functionally Substituted Chalcones and Their Derivatives
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Functionally substituted chalcones, pyrazolines, and flavonones have been synthesized. Their structure has been studied by means of 1H and 13C NMR spectroscopy, including COSY and HMQC experiments. Anti-inflammatory activity of the s
- Nurkenov,Ibraev,Schepetkin,Khlebnikov,Seilkhanov,Arinova,Isabaeva
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p. 1360 - 1367
(2019/08/21)
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- Design, Synthesis, and Biological Evaluation of Novel Allosteric Protein Disulfide Isomerase Inhibitors
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Protein disulfide isomerase (PDI) is responsible for nascent protein folding in the endoplasmic reticulum (ER) and is critical for glioblastoma survival. To improve the potency of lead PDI inhibitor BAP2 ((E)-3-(3-(4-hydroxyphenyl)-3-oxoprop-1-en-1-yl)benzonitrile), we designed and synthesized 67 analogues. We determined that PDI inhibition relied on the A ring hydroxyl group of the chalcone scaffold and cLogP increase in the sulfonamide chain improved potency. Docking studies revealed that BAP2 and analogues bind to His256 in the b′ domain of PDI, and mutation of His256 to Ala abolishes BAP2 analogue activity. BAP2 and optimized analogue 59 have modest thiol reactivity; however, we propose that PDI inhibition by BAP2 analogues depends on the b′ domain. Importantly, analogues inhibit glioblastoma cell growth, induce ER stress, increase expression of G2M checkpoint proteins, and reduce expression of DNA repair proteins. Cumulatively, our results support inhibition of PDI as a novel strategy to treat glioblastoma.
- Yang, Suhui,Shergalis, Andrea,Lu, Dan,Kyani, Anahita,Liu, Ziwei,Ljungman, Mats,Neamati, Nouri
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p. 3447 - 3474
(2019/04/16)
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- Novel chalcone derivatives containing a 1,2,4-triazine moiety: Design, synthesis, antibacterial and antiviral activities
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A series of novel chalcone derivatives containing the 1,2,4-triazine moiety were synthesized and their structures were confirmed by 1H NMR, 13C NMR and elemental analyses. Antiviral bioassays revealed that most of the compounds exhibited good antiviral activity against tobacco mosaic virus (TMV) at a concentration of 500 μg mL-1. The designated compound 4l was 50% effective in terms of curative and protective activities against TMV with 50% effective concentrations (EC50) of 10.9 and 79.4 μg mL-1, which were better than those of ningnanmycin (81.4 and 82.2 μg mL-1). Microscale thermophoresis (MST) also showed that the binding of compound 4l to coat protein (TMV-CP) yielded a Kd value of 0.275 ± 0.160 μmol L-1, which was better than that of ningnanmycin (0.523 ± 0.250 μmol L-1). At the same time, molecular docking studies for 4l with TMV-CP (PDB code:1EI7) showed that the compound was embedded well in the pocket between the two subunits of TMV-CP. Meanwhile, compound 4a demonstrated excellent antibacterial activities against Ralstonia solanacearum (R. solanacearum), with an EC50 value of 0.1 μg mL-1, which was better than that of thiodiazole-copper (36.1 μg mL-1) and bismerthiazol (49.5 μg mL-1). The compounds act by causing folding and deformation of the bacterial cell membrane as observed using scanning electron microscopy (SEM). The chalcone derivatives thus synthesized could become potential alternative templates for novel antiviral and antibacterial agents.
- Tang, Xu,Su, Shijun,Chen, Mei,He, Jun,Xia, Rongjiao,Guo, Tao,Chen, Ying,Zhang, Cheng,Wang, Jun,Xue, Wei
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p. 6011 - 6020
(2019/03/12)
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- Synthesis and antibacterial evaluation of novel chalcone derivatives containing a benzothiazole scaffold
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Abstract: A series of novel chalcone derivatives containing a benzothiazole scaffold were synthesized to develop novel antibacterial agents for solving the problem of drug resistance. Most compounds exhibited excellent antibacterial activity against Xanthomonas oryzae pv. Oryzae (Xoo), Xanthomonas axonopodis pv. Citri (Xac), and Ralstonia solanacearum (Rs) compared to a reference drug, bismerthiazol. The results indicated that chalcone derivatives containing a benzothiazole scaffold merit more research as promising antibacterial agents. Graphical abstract: [Figure not available: see fulltext.].
- Wang, Yihui,Li, Pu,Jiang, Shichun,Chen, Ying,Su, Shijun,He, Jun,Chen, Mei,Zhang, Juping,Xu, Weiming,He, Ming,Xue, Wei
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- Antimicrobial evaluation and action mechanism of chalcone derivatives containing quinoxaline moiety
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Abstract: A series of chalcone derivatives containing quinoxaline moieties were synthesized, and their antibacterial activities were evaluated. Antibacterial bioassays indicated that some of the compounds exhibited significant antibacterial activity against Xanthomonas axonopodis pv. Citri (Xac), Xanthomonas oryzae pv. oryzae (Xoo), and Ralstonia solanacearum (Rs) at the concentrations of 50 or 100?μg/cm3. 50% effective concentration (EC50) values of (E)-3-(pyridin-2-yl)-1-[4-(quinoxalin-2-yloxy)phenyl]prop-2-en-1-one against Xac, Xoo, and Rs were 6.72, 15.17, and 9.29?μg/cm3, respectively, which were better than those of bismerthiazol (44.31, 42.46, and 62.36?μg/cm3, respectively). Scanning electron microscopy (SEM) was employed to analyze the mechanism of antibacterial action of that compound toward Xac. Graphical abstract: [Figure not available: see fulltext.].
- Xia, Rongjiao,Guo, Tao,He, Jun,Chen, Mei,Su, Shijun,Jiang, Shichun,Tang, Xu,Chen, Ying,Xue, Wei
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p. 1325 - 1334
(2019/07/03)
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- Structure-activity relationship with pyrazoline-based aromatic sulfamates as carbonic anhydrase isoforms I, II, IX and XII inhibitors: Synthesis and biological evaluation
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Four new series of aromatic sulfamates were synthesized and investigated for the inhibition of four human (h) isoforms of zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), hCA I, II, IX, and XII. The reported derivatives, obtained by a sulfamoylation reaction of the corresponding phenolic precursors, bear 3,5-diarylpyrazoline moieties as spacers between the benzenesulfamate fragment which binds the zinc ion from the active site, and the tail of the inhibitor. Pyrazolines are biologically privileged scaffolds, endowed with versatile biological activity, such as an anti-proliferative action. The derivatives were tested for the inhibition of the cytosolic, hCA I and II (off target isoforms) and the trans-membrane, tumor-associated hCA IX and XII enzymes (anticancer drug targets). Generally, hCA I was not effectively inhibited, whereas many low nanomolar inhibitors were evidenced against hCA II (KIs in the range of 0.42–90.1 nM), IX (KIs in the range of 0.72–63.6 nM), and XII (KIs in the range of 0.88–85.2 nM). The best substitution fragments at the pyrazoline ring included for CA II a 4-sulfamic group on the 3-aryl and halogens on the 5-aryl or a methoxy group on the 3-aryl and a 4-sulfamate group on the 5-aryl; for CA IX and CA XII they included the sulfamic group on the 3- or 4-position of the 5-aryl and an electronwithdrawing group on the 4-postion of the 3-aryl ring.
- Moi, Davide,Nocentini, Alessio,Deplano, Alessandro,Balboni, Gianfranco,Supuran, Claudiu T.,Onnis, Valentina
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- TOLL-LIKE RECEPTOR SIGNALING INHIBITORS
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Di- and triaryl-substituted heteroaromatic compounds have Toll-like receptor inhibitory activity, including at TLR2, TLR4, TLR7, and/or TLR9. Compounds and compositions have applications in the treatment of diseases and conditions mediated by Toll-like receptors and related receptors, such as bacterial sepsis, autoimmune disease, lupus erythematosus, ischemia-reperfusion injury, stroke, metabolic disease, obesity-related metabolic inflammation, gout, and cancer.
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Paragraph 00256
(2019/07/20)
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- Discovery of novel human inosine 5′-monophosphate dehydrogenase 2 (hIMPDH2) inhibitors as potential anticancer agents
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The enzyme inosine 5′-monophosphate dehydrogenase (IMPDH) catalyzes an essential step in the de novo biosynthesis of guanine nucleotides, and thus regulates the guanine nucleotide pool required for cell proliferation. Of the two isoforms, human IMPDH type 2 (hIMPDH2) is a validated molecular target for potential immunosuppressive, antiviral and anticancer chemotherapy. In search of newer hIMPDH2 inhibitors as potential anticancer agents, three novel series (A: 5-aminoisobenzofuran-1(3H)-one, B: 3,4-dimethoxyaniline and C: benzo[d]-[1,3]dioxol-5-ylmethanamine) were synthesized and evaluated for in vitro and cell-based activities. A total of 37 molecules (29–65) were screened for their in vitro hIMPDH2 inhibition, with particular emphasis on establishing their structure–activity relationship (SAR) trends. Eight compounds (hits, 30, 31, 33–35, 37, 41 and 43) demonstrated significant enzyme inhibition (>70% @ 10 μM); especially the A series molecules were more potent than B series (50 values for the hits ranged from 0.36 to 7.38 μM. The hits displaying >80% hIMPDH2 inhibition (30, 33, 35, 41 and 43) were further assessed for their cytotoxic activity against cancer cell lines such as MDA-MB-231 (breast adenocarcinoma), DU145 (prostate carcinoma), U87 MG (glioblastoma astrocytoma) and a normal cell line, NIH-3T3 (mouse embryonic fibroblast) using MTT assay. Most of the compounds exhibited higher cellular potency against cancer cell lines and notably lower toxicity towards NIH-3T3 cells compared to mycophenolic acid (MPA), a prototypical hIMPDH2 inhibitor. Two of the series A hits (30 and 35) were evaluated in human peripheral blood mononuclear cells (hPBMC) assay and found to be better tolerated than MPA. The calculated/predicted molecular and physicochemical properties were satisfactory with reference to drug-likeness. The molecular docking studies clearly demonstrated crucial interactions of the hits with the cofactor-binding site of hIMPDH2, further providing critical information for refining the design strategy. The present study reports the design and discovery of structurally novel hIMPDH2 inhibitors as potential anticancer agents and provides a guide for further research on the development of safe and effective anticancer agents, especially against glioblastoma.
- Shah, Chetan P.,Kharkar, Prashant S.
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p. 286 - 301
(2018/09/18)
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- Solvent and substituent effect on the photophysical properties of pyrazoline derivatives: A spectroscopic study
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Pyrazoline derivatives are among solvatochromic dyes and they are the most widely used in many fields such as sensors, labeling agent and optoelectronic devices. Therefore, synthesis of new pyrazoline derivatives and determination of their optical behavior in different solvents are a very important research area. In this study, the solvatochromic behaviors of seven new synthetic pyrazoline derivatives, (4-[3-(4-Hydroxyphenyl)-5-aryl-4,5-dihydro-pyrazol-1-yl]benzenesulfonamides, compound 1-7), were determined in different solvents. As a result of the measurements, a large red shifts in the fluorescence spectra of the compounds studied were observed for each compound, when the polarity of the solvent increased. Kamlet-Taft and Catalan parameters were used to describe the solvent-soluble interactions. The obtained results showed that the solvatochromic behavior of the compounds is dependent on their solvent polarity as well as the effect of the hydrogen-bonding properties of the solvents. It was also found that the increases in the polarity of the solvent was facilitated the non-radiative transition. Furthermore, the changes in the dipole moments of compounds 1-7 in different solvents at room temperature were calculated by using the Lippert–Mataga equation. It was very impressive that calculated fluorescence quantum yield values of the compounds studied here by using different solvents were remarkably high than the ones reported in the literatures for pyrazolines. In addition, the effect of substituent on the photo-physical properties of the compounds was also investigated. It was observed that the fluorescence intensity of the substituted compounds 2-6 increased comparing to the compound 1, which is a non-substituted derivative. These changes were not dependent on electronic nature of the substituent on phenyl ring (i.e. electron donating and electron withdrawing substituent). According to data obtained it can be stated that these novel solvatochromic dyes studied here can be find application in pharmaceutical industry, as labeling agent, sensor applications as biosensors or analytical sensors and/or optoelectronic devices.
- Bozkurt, Ebru,Gul, Halise Inci,Mete, Ebru
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- Triaryl Pyrazole Toll-Like Receptor Signaling Inhibitors: Structure–Activity Relationships Governing Pan- and Selective Signaling Inhibitors
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The immune system uses members of the toll-like receptor (TLR) family to recognize a variety of pathogen- and host-derived molecules in order to initiate immune responses. Although TLR-mediated, pro-inflammatory immune responses are essential for host defense, prolonged and exaggerated activation can result in inflammation pathology that manifests in a variety of diseases. Therefore, small-molecule inhibitors of the TLR signaling pathway might have promise as anti-inflammatory drugs. We previously identified a class of triaryl pyrazole compounds that inhibit TLR signaling by modulation of the protein–protein interactions essential to the pathway. We have now systematically examined the structural features essential for inhibition of this pathway, revealing characteristics of compounds that inhibited all TLRs tested (pan-TLR signaling inhibitors) as well as compounds that selectively inhibited certain TLRs. These findings reveal interesting classes of compounds that could be optimized for particular inflammatory diseases governed by different TLRs.
- Pollock, Julie A.,Sharma, Naina,Ippagunta, Sirish K.,Redecke, Vanessa,H?cker, Hans,Katzenellenbogen, John A.
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p. 2208 - 2216
(2018/09/25)
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- Cinnamoylated chloroquine analogues: A new structural class of antimalarial agents
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A novel series of cinnamoylated chloroquine hybrid analogues were synthesized and evaluated as antimalarial agents. The trans cinnamic acid derivatives (3–8) were synthesized by utilizing substituted aldehydes and malanoic acid in DMF catalysed by DABCO. The final cinnamoylated chloroquine analogues (9–14) were synthesized by utilizing DCC coupling reagent. The amido chloroquine (17) was prepared from acid (16) and compound 2 in benzene using SOCl2 as chlorinating agent. The corresponding ester (15) was prepared from 2-hydroxy acetophenone and 2-bromoacetates in actonitrile in presence of K2CO3?as?base followed by basic hydrolysis. The preparation of amide based chloroquine-chalcone analogues (18–22), were obtained by the combination of amido chloroquine (17) and aldehydes in 10% aq. KOH in methanol at room temperature. Further we prepared epichlorohydrin based chloroquine-chalcone analogues (25–28), by reacting the epoxide (24a, 24b and 24c) with 2 and methelenedioxy aniline. In?vitro antimalarial activity against chloroquine sensitive strain 3D7, chloroquine resistant strain K1 of P.?falciparum and in?vitro cytotoxicity of compounds using VERO cell line was carried out. The synthesized molecules showed significant in?vitro antimalarial activity especially against CQ resistant strain (K1). Among tested compounds, 13, 9 and 10 were found to be the most potent compounds of the series with IC50 value of 44.06, 48.04 and 59.37?nM against chloroquine resistant K1 strain.
- Gayam, Venkatareddy,Ravi, Subban
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p. 382 - 391
(2017/05/04)
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- Nonlinear optical studies and structure-activity relationship of chalcone derivatives with in silico insights
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Nine chalcones were prepared via Claisen-Schmidt condensation, and characterized by UV–vis, IR1H NMR13C NMR and mass spectrometry. One of the representative member 4-NDM-TC has been studied via single crystal XRD and the TGA/DTA tech
- Kar, Swayamsiddha,Adithya,Shankar, Pruthvik,Jagadeesh Babu,Srivastava, Sailesh,Nageswara Rao
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p. 294 - 302
(2017/03/24)
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- CBr4 as a Halogen Bond Donor Catalyst for the Selective Activation of Benzaldehydes to Synthesize α,β-Unsaturated Ketones
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CBr4 has been employed as a halogen bond donor catalyst for the selective activation of aldehyde, to achieve an efficient solvent- and metal-free CC bond forming reaction in the presence of strong acid sensitive groups such as methoxy, cyanide, ester, and ketal for the synthesis of α,β-unsaturated ketones. This unique capability of CBr4 to act as a halogen bond donor has been explored and established using UV-vis as well as IR spectroscopy. Moreover, this unprecedented methodology enables the synthesis of the pharmaceutically important molecule licochalcone A.
- Kazi, Imran,Guha, Somraj,Sekar, Govindasamy
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supporting information
p. 1244 - 1247
(2017/03/14)
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- Novel trans-Ferulic Acid Derivatives Containing a Chalcone Moiety as Potential Activator for Plant Resistance Induction
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A series of novel trans-ferulic acid derivatives containing a chalcone moiety were designed and synthesized to induce plant resistance. Antiviral activities of the compounds were evaluated. Bioassay results demonstrated that compounds F3, F6, F17, and F27 showed remarkable curative, protective, and inactivating activities against tobacco mosaic virus (TMV). With a 50% effective concentration (EC50) value of 98.78 μg mL-1, compound F27 exhibited the best protective activity compared with trans-ferulic acid (328.6 μg mL-1), dufulin (385.6 μg mL-1), and ningnanmycin (241.3 μg mL-1). This protective ability was associated with potentiation of defense-related enzyme activity and activation of photosynthesis of tobacco at an early stage. This notion was confirmed by up-regulated expression of stress responses and photosynthesis regulating proteins. This work revealed that F27 can induce resistance and enhance plant tolerance to TMV infection. Hence, F27 can be considered as a novel activator for inducing plant resistance.
- Gan, Xiuhai,Hu, Deyu,Wang, Yanjiao,Yu, Lu,Song, Baoan
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p. 4367 - 4377
(2017/06/13)
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- An aza-BODIPY based near-infrared fluorescent probe for sensitive discrimination of cysteine/homocysteine and glutathione in living cells
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Discriminative detection of glutathione (GSH) from cysteine/homocysteine (Cys/Hcy) is achieved through two emission channel analysis using a stable, highly sensitive, and selective near-infrared fluorescent probe that bears 7-nitrobenzo-2-oxa-1,3-diazole
- Xiang, Hui-Jing,Tham, Huijun Phoebe,Nguyen, Minh Duc,Fiona Phua, Soo Zeng,Lim, Wei Qi,Liu, Jin-Gang,Zhao, Yanli
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supporting information
p. 5220 - 5223
(2017/07/12)
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- Synthesis of 1,3,5-trisubstituted pyrazolines as potential antimalarial and antimicrobial agents
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A series of novel 1,3,5-trisubstituted pyrazolines derivatives have been synthesized from chalcones and nicotinic acid hydrazide in two steps. In first step, chalcones were prepared by treatment of 4-hydroxy acetophenone with different substituted benzald
- Mishra, Vikash K.,Mishra, Mitali,Kashaw, Varsha,Kashaw, Sushil K.
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p. 1949 - 1962
(2017/03/08)
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- Designing, synthesis and bioactivities of 4-[3-(4-hydroxyphenyl)-5-aryl-4,5-dihydro-pyrazol-1-yl]benzenesulfonamides
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In this study, 4-[3-(4-hydroxyphenyl)-5-aryl-4,5-dihydro-pyrazol-1-yl]benzenesulfonamide (1–9) types compounds were synthesized and their chemical structures were confirmed by 1H NMR, 13C NMR and HRMS spectra. Cytotoxic and carbonic anhydrase (CA) inhibitory effects of the compounds were investigated. Cytotoxicity experiments pointed out that compound 4, (4-[5-(4-chlorophenyl)-3-(4-hydroxyphenyl)-4,5-dihydro-pyrazol-1-yl]benzenesulfonamide), exerting the highest tumor selectivity (TS) and potency selectivity expression (PSE) values, can be considered as a lead compound of this study in terms of development of novel anticancer agents. All synthesized sulfonamides showed a good inhibition profile on hCA IX and XII in the range of 53.5–923 nM and 6.2–95 nM, respectively. These compounds were 2.5–13.4 times more selective for the inhibition of hCA XII versus hCA IX, except compound 2 which had similar inhibitory action towards both isoenzymes.
- Gul, Halise Inci,Eren, Sakip Emre,Yamali, Cem,Mete, Ebru,Sakagami, Hiroshi,Supuran, Claudiu T.
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p. 169 - 175
(2017/11/21)
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- Design, synthesis, and antiviral activities of 1,5-benzothiazepine derivatives containing pyridine moiety
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In our previous work, a series of novel benzothiazepine derivatives containing pyridine moiety were successfully synthesized through chalcone 1,3-dipolar cycloaddition and determined their antiviral activity against tobacco mosaic virus (TMV). Bioassay results indicated that most of these target compounds exhibited improved curative, protection, and inactivation activity in?vivo than the commercial agent ningnanmycin. Particularly, compound 3m exhibited marked curative activity against TMV, with an EC50value of 352.2?μM, which was even better than that of ningnanmycin. The compound was identified as the most promising candidate for inhibiting plant virus and an excellent compound with antiviral activities against TMV. Structure–activity relationship experiment indicated that the 1,5-benzothiazepine moiety is crucial for potent anti-TMV activity.
- Li, Tianxian,Zhang, Jian,Pan, Jianke,Wu, Zengxue,Hu, Deyu,Song, Baoan
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p. 657 - 662
(2016/10/14)
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- Design, synthesis and in vitro evaluation of some small molecules malonyl CoA decarboxylase inhibitors containing pyrazoline scaffold and study of their binding interactions with malonyl CoA decarboxylase via preliminary docking simulation
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In the present work series of small molecules (5a–5m, 6a–6j) were schematically designed and synthesized using simple chemical procedures. Their structures were confirmed based upon findings from infrared, 1H nuclear magnetic resonance (NMR), 13C NMR, and mass spectra. The derivatives were evaluated for their in vitro malonyl CoA decarboxylase inhibition activity by using fluorimetric assay. Pyrazol-1-yl-1, 3-thaizol-4(5H)-one derivative (5a–5m) showed better activity than pyrazol-1-yl-1-ethanone derivatives (6a–6j). Compounds 5e, 5j, and 6f showed an excellent in vitro malonyl CoA decarboxylase inhibition activity with IC50 value 0.10, 0.27, and 0.26 μM, respectively. These most active compounds 5e, 5j, and 6f were docked into malonyl-CoA decarboxylase (HsMCD, PDB ID: 2YGW) to study ligand–protein interaction.
- Jagdale, Deepali M.,Ramaa
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p. 2127 - 2140
(2017/08/03)
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- Synthesis, structural and thermal characterizations and in vitro cytotoxic activities of new cyclotriphosphazene derivatives
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We investigated the cytotoxic effects of the newly synthesized cyclotriphosphazene derivatives on A2780 (ovarian), PC-3 and LNCaP (prostate) cancer cell lines. 4′-hydroxy-supstituted-chalcone compounds (2–8) were reacted with diphenyl-cyclotriphosphazene (DPP) in the presence of acetone/K2CO3 in order to obtain novel cyclotriphosphazene compounds (DPP 2–8). The structures of DPP 2–8 were characterized by MALDI-TOF mass spectrometry, FT-IR, elemental analysis, 1H, 13C-APT, and 31P NMR measurements. The thermal properties of all phosphazene compounds have been studied after synthesis and characterization procedure. The cytotoxic effects of DPP 2–8 were examined primarily by applying the MTT method based on the measurement of mitochondrial activity. In this regard, several phosphazene compounds have shown high chemotherapeutic effect at low dose (p 50 values (p 0.05). The compounds DPP 2–8 possess cytotoxic activity against PC-3 and LNCaP cells (especially compounds DPP-4 and DPP-5, p 0.05).
- Koran, Kenan,Tekin, ?i?dem,?al??kan, Eray,Tekin, Suat,Sandal, Süleyman,G?rgülü, Ahmet Orhan
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p. 1002 - 1011
(2017/09/08)
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- Synthesis, anticancer evaluation and pharmacokinetic study of novel 10-O-phenyl ethers of dihydroartemisinin
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Twenty hybrid compounds, tethering dihydroartemisinin (DHA) with diaryl-pyrazoline/diaryl-pyrazole through ether linkage, were synthesized based on hybridization strategy and assessed for their anticancer activity. The representative compound 6f exhibited significantly elevated antiproliferative activity compared with DHA against a panel of cancer cell lines. Unexpected sensitivity of 6f in Adriamycin-resistant MCF-7 cells (MCF-7/Adr) inspired subsequent research on anticancer activity of these DHA derivatives against breast cancer cell lines. All the novel compounds exhibited potent activity in three breast cancer cells including MDA-MB-231, MCF-7 and MCF-7/Adr. Most of them exerted almost 10-fold higher potency in MCF-7/Adr than in MCF-7 and MDA-MB-231 cells. Compound 5f, the most potent compound against MCF-7/Adr (GI50 = 18 nM), was used for mechanism research which revealed that compound 5f arrested MCF-7 and MCF-7/Adr cells in G0/G1 phase with decreased levels of cyclin D1 and increased levels of p27. Preliminary pharmacokinetic properties of 5f and 6f were investigated in rats after a single intravenous administration. The high sensitivity of MCF-7/Adr indicates that these compounds have potential to be developed as therapeutic agents to treat drug-resistant cancer.
- Luan, Shenglin,Zhong, Hang,Zhao, Xuan,Yang, Jinyu,Jing, Yongkui,Liu, Dan,Zhao, Linxiang
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supporting information
p. 584 - 595
(2017/11/14)
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- Design, synthesis, biological evaluation, and molecular modeling studies of chalcone-rivastigmine hybrids as cholinesterase inhibitors
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A series of novel chalcone-rivastigmine hybrids were designed, synthesized, and tested in vitro for their ability to inhibit human acetylcholinesterase and butyrylcholinesterase. Most of the target compounds showed hBChE selective activity in the micro- a
- Wang, Ling,Wang, Yu,Tian, Yiguang,Shang, Jinling,Sun, Xiaoou,Chen, Hongzhuan,Wang, Hao,Tan, Wen
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p. 360 - 371
(2016/12/22)
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- Facile One-Pot Synthesis Methodology for Nitrogen-Containing Heterocyclic Derivatives of 3,5-Disubstituted 4,5-Dihydro-1H-Pyrazole, Their Biological Evaluation and Molecular Docking Studies
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A series of 2-pyrazoline derivatives (PS-1 to PS-16) were synthesized by reacting different aromatic/heteroaromatic aldehydes and ketones, in a two-step reaction through Claisen – Schmidt condensation, followed by cyclization of the resulting chalcones wi
- Upadhyay, Savita,Tripathi, Avinash C.,Paliwal, Sarvesh,Saraf, Shailendra K.
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p. 564 - 575
(2017/11/10)
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- A Green, Solvent-Free, Microwave-Assisted, High-Yielding YbCl3Catalyzed Deprotection of THP/MOM/Ac/Ts Ethers of Chalcone Epoxide and 2′-Aminochalcone and Their Sequel Cyclization
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Under microwave and solvent-free conditions, YbCl3efficiently catalyzed the deprotection of tetrahydropyran-2-yl, methoxymethyl (MOM), acetyl, and tosyl groups and sequel cyclization of chalcone epoxide to 2-hydroxyindanone and 2′-aminochalcone to aza-flavanone. The reaction afforded the products in excellent yield (78–99%) at 850 W microwave heating within 1–5 min under eco-friendly conditions. The merits of the presented protocol include high yield, use of microwave irradiation, solvent-free condition, catalyst reusability, and no need for purification with column chromatography. The present method is very much milder but more advanced than those reported earlier.
- Kumar, Sumit,Verma, Nishant,Parveen, Iram,Ahmed, Naseem
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supporting information
p. 2111 - 2122
(2016/11/23)
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- Synthesis, antiviral activity, 3D-QSAR, and interaction mechanisms study of novel malonate derivatives containing quinazolin-4(3H)-one moiety
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A series of novel malonate derivatives containing quinazolin-4(3H)-one moiety were synthesized and evaluated for their antiviral activities against cucumber mosaic virus (CMV). Results indicated that the title compounds exhibited good antiviral activities. Notably, compounds g15, g16, g17, and g18 exhibited excellent curative activities in vivo against CMV, with 50% effective concentration (EC50) values of 208.36, 153.78, 181.47, and 164.72 μg/mL, respectively, which were better than that of Ningnanmycin (256.35 μg/mL) and Ribavirin (523.34 μg/mL). Moreover, statistically valid three-dimensional quantitative structure-activity relationship (3D-QSAR) models with good correlation and predictive power were obtained with comparative molecular field analysis (CoMFA) steric and electrostatic fields (r2 = 0.990, q2 = 0.577) and comparative molecular similarity indices analysis (CoMSIA) with combined steric, electrostatic, hydrophobic and hydrogen bond acceptor fields (r2 = 0.977, q2 = 0.516), respectively. Based on those models, compound g25 was designed, synthesized, and showed better curative activity (146.30 μg/mL) than that of compound g16. The interaction of between cucumber mosaic virus coat protein (CMV CP) and g25 with 1:1.83 ratio is typically spontaneous and exothermic with micromole binding affinity by isothermal titration calorimetry (ITC) and fluorescence spectroscopy investigation.
- Chen, Meihang,Li, Pei,Hu, Deyu,Zeng, Song,Li, Tianxian,Jin, Linhong,Xue, Wei,Song, Baoan
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supporting information
p. 168 - 173
(2015/12/20)
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- DARC: Mapping Surface Topography by Ray-Casting for Effective Virtual Screening at Protein Interaction Sites
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Protein-protein interactions represent an exciting and challenging target class for therapeutic intervention using small molecules. Protein interaction sites are often devoid of the deep surface pockets presented by "traditional" drug targets, and crystal structures reveal that inhibitors typically engage these sites using very shallow binding modes. As a consequence, modern virtual screening tools developed to identify inhibitors of traditional drug targets do not perform as well when they are instead deployed at protein interaction sites. To address the need for novel inhibitors of important protein interactions, here we introduce an alternate docking strategy specifically designed for this regime. Our method, termed DARC (Docking Approach using Ray-Casting), matches the topography of a surface pocket "observed" from within the protein to the topography "observed" when viewing a potential ligand from the same vantage point. We applied DARC to carry out a virtual screen against the protein interaction site of human antiapoptotic protein Mcl-1 and found that four of the top-scoring 21 compounds showed clear inhibition in a biochemical assay. The Ki values for these compounds ranged from 1.2 to 21 μM, and each had ligand efficiency comparable to promising small-molecule inhibitors of other protein-protein interactions. These hit compounds do not resemble the natural (protein) binding partner of Mcl-1, nor do they resemble any known inhibitors of Mcl-1. Our results thus demonstrate the utility of DARC for identifying novel inhibitors of protein-protein interactions.
- Gowthaman, Ragul,Miller, Sven A.,Rogers, Steven,Khowsathit, Jittasak,Lan, Lan,Bai, Nan,Johnson, David K.,Liu, Chunjing,Xu, Liang,Anbanandam, Asokan,Aubé, Jeffrey,Roy, Anuradha,Karanicolas, John
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supporting information
p. 4152 - 4170
(2016/06/01)
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- Design, synthesis and antiproliferative activity studies of novel dithiocarbamate–chalcone derivates
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A series of novel dithiocarbamate–chalcone derivates were designed, synthesized and evaluated for antiproliferative activity against three selected cancer cell lines (EC-109, SK-N-SH and MGC-803). Majority of the synthesized compounds exhibited moderate t
- Fu, Dong-Jun,Zhang, Sai-Yang,Liu, Ying-Chao,Zhang, Li,Liu, Jun-Ju,Song, Jian,Zhao, Ruo-Han,Li, Feng,Sun, Hui-Hui,Liu, Hong-Min,Zhang, Yan-Bing
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supporting information
p. 3918 - 3922
(2016/08/01)
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- Eu+3-doped chalcone substituted cyclotriphosphazenes: Synthesis, characterizations, thermal and dielectrical properties
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A series of new cyclotriphosphazene derivatives (2a-e) were prepared from the reactions of substituted chalcone compounds (1a-e) containing different organic side groups at para position with cyclotriphosphazene (2) bearing dioxybiphenyl. The structures of 2a-e were approved by microanalysis and spectroscopic techniques (MS, FT-IR, 31P, 1H, 13C, and 13C-APT NMR). The thermal behaviors of compounds 2a-e were investigated by thermogravimetric analysis (TGA). These compounds were found to be stable up to about 300 °C. Dielectric properties of 2a-e were measured against temperature (between 25 and 160 °C at 1 kHz) and frequency (range from 100 Hz to 5 kHz at 25 °C) using means of an impedance analyzer. Among them dielectric properties of methoxy substituted cyclotriphosphazene 2e were found to be higher than other phosphazenes. The compound 2b, which has the lower dielectric property values than other phosphazenes, was selected to determine the influence of Eu+3-doping on the dielectric properties of phosphazenes and doped with Eu+3 at different mole ratios. At the dielectric properties of Eu+3-doped compound 2b (with increasing molar ratios of Eu+3) was observed an excellent increasing according to Eu+3-undoped phosphazene compounds.
- Koran, Kenan,?zen, Furkan,Biryan, Fatih,Demirelli, Kadir,G?rgülü, Ahmet Orhan
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p. 162 - 169
(2016/06/09)
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- One-Pot Three-Component Synthesis of 2-Amino Pyrimidines in Aqueous PEG-400 at Ambient Temperature
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Amino pyrimidines have been synthesized by a one-pot procedure under environmentally friendly reaction conditions at room temperature. The use of aqueous PEG-400 circumvents the problems associated with the toxic, hazardous organic solvents and oxidizing agents.
- Jawale, Dhanaji V.,Pratap, Umesh R.,Bhosale, Manisha R.,Mane, Ramrao A.
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p. 1626 - 1630
(2016/09/23)
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- Niacin esters of chalcones with tumor-selective properties
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Novel series of niacin esters of chalcones 2, 4 and 6 were designed as antineoplastic agents that have the potential to release the chemoprotectant niacin. These enones are cytotoxic to human CD4 +T-lymphocyte Molt 4/C8 and CEM and murine leukemia L1210 cells. Quantitative structure–activity relationship (QSAR) studies of the biodata in series 4 revealed that cytotoxic potency was enhanced by placing electron-repelling groups in one of the aryl rings. The compounds are lethal to HL-60, HSC-2, HSC-3 and HSC-4 neoplasms but less toxic to nonmalignant hepatocyte growth factor, hematopoietic progenitor cell and human periodontal ligament fibroblast cells. Hence, the compounds display tumor-selective toxicity. These chalcones are well tolerated in mice and no overt toxicity was noted. The results establish that in general the compounds in series 2, 4 and 6 have positive characteristics which warrant further studies.
- Panda, Atulya K.,Das, Umashankar,Roayapalley, Praveen K.,Sakagami, Hiroshi,Kawase, Masami,Balzarini, Jan,De Clercq, Erik,Dimmock, Jonathan R.
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p. 1451 - 1456
(2016/10/09)
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- A kind of carbamate-koncar ketone choline esterase inhibitor and its preparation method and application (by machine translation)
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The present invention discloses a kind of carbamate-koncar ketone choline esterase inhibitor and its preparation method and application, belongs to the field of medicinal chemistry. Cholinesterase inhibitors of the invention represented by general formula
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Paragraph 0171; 0172; 0173
(2016/11/28)
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- β-Cyclodextrin/IBX in water: Highly facile biomimetic one pot deprotection of THP/MOM/Ac/Ts ethers and concomitant oxidative cleavage of chalcone epoxides and oxidative dehydrogenation of alcohols
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A mild and efficient one-pot deprotection of THP/MOM/Ac/Ts ethers, and concomitant oxidative cleavage of epoxides and oxidative dehydrogenation of alcohols to form β-hydroxy 1,2-diketones, 1,2,3-triketones and conjugated aromatic carbonyl systems (chalcones) using β-cyclodextrin/IBX in water has been developed. o-Iodoxybenzoic acid, a readily available hypervalent iodine(v) reagent, was found to be highly effective with β-cyclodextrin in carrying out the deprotection and subsequent transformations under an eco-friendly environment. The reaction gave moderate to excellent yields ranging from 50-99% at 60°C in 40 min to 6 h.
- Kumar, Sumit,Ahmed, Naseem
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supporting information
p. 648 - 656
(2016/02/12)
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- Catalyzed Claisen-Schmidt reaction by protonated aluminate mesoporous silica nanomaterial focused on the (E)-chalcone synthesis as a biologically active compound
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The mesoporous silica structure (MSN) was synthesized using the sol-gel method followed by aluminum grafting and protonation and was then denoted as HAlMSN (Si/Al = 18.9). N2 physisorption confirmed the mesoporous structure with a pore diameter of 3.38 nm. 27Al NMR showed the presence of framework and extra-framework aluminum structures, which led to the formation of strong Lewis and Br?nsted acidic sites. HAlMSN catalyzed the synthesis of (E)-chalcones through the Claisen-Schmidt reaction. Chalcone derivatives have been applied as biologically active compounds with anti-cancer, anti-inflammatory and diuretic pharmacological activities. The products were obtained via reactions on the protonic acid sites of HAlMSN. The significant advantages of this reaction are high yield, easy work up, short reaction time and also compatibility with various organic solvents. The products were obtained in an excellent conversion of 97% at 298 K. The results show that the electron donating substituents exhibit higher conversion in comparison to electron withdrawing substituents. The stability of the catalyst was investigated by reusing it five times for (E)-chalcone production and there was only a slight decrease in its catalytic activity. The highest product of (E)-chalcone was observed with a 1:2 molar ratio of benzaldehyde/acetophenone. A comparative study in chalcone synthesis using the heterogeneous catalysts demonstrated that HAlMSN has a significantly high activity at low temperature.
- Sazegar, Mohammad Reza,Mahmoudian, Shaya,Mahmoudi, Ali,Triwahyono, Sugeng,Jalil, Aishah Abdul,Mukti, Rino R.,Nazirah Kamarudin, Nur H.,Ghoreishi, Monir K.
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p. 11023 - 11031
(2016/02/05)
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- Pyridine-containing benzothiazepine derivatives, and preparation method and application thereof
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The invention discloses pyridine-containing benzothiazepine derivatives, and a preparation method and application thereof. The general formula (I) of the derivatives is described in the specification. In the formula (I), R is selected from a group consisting of a phenyl group, a 4-methylphenyl group, a thien-2-yl gourp, a 4-methoxyphenyl group, a 4-nitrophenyl group, a 4-trifluoromethoxyphenyl group, a 4-bromophenyl group, a furan-2-yl group, a 4-fluorophenyl group, a 3,4-dimethyoxyphenyl group, a 2-chlorophenyl group, a 2-phenyl group, a 3-bromophenyl group, a 2-methyoxyphenyl group, a 2-fluorophenyl group, a 3-methyoxyphenyl group, a 4-trifluoromethylphenyl group, a 2-trifluoromethylphenyl group, a 4-chlorophenyl group, a 3-fluorophenyl group, a 2,4-dichlorophenyl group, a 3,4-dichlorophenyl group, a 2,6-dichlorophenyl group, a 2-chloro-6-fluorophenyl group, a 3-nitrophenyl group and a naphtha-1-yl group. According to the invention, synthesis route is simple; yield is high; and plant virus diseases can be efficiently and safely prevented and controlled.
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Paragraph 0015; 0024
(2016/10/10)
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- β-Cyclodextrin in water: Highly facile biomimetic one pot deprotection of phenolic THP/MOM/Ac/Ts ethers and concomitant regioselective cyclization of chalcone epoxides and 2′-aminochalcones
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A mild and efficient one-pot deprotection of THP/MOM/Ac/Ts ethers and the concomitant cyclization of chalcone epoxides to 2-hydroxyindanones or 2′-aminochalcones to aza-flavanones using β-cyclodextrin in water has been developed. β-CD was found to be highly effective at carrying out the deprotection and sequential transformations in an eco-friendly environment affording moderate to excellent yields (59-99%) at 60 °C in 8-22 min. Water, an eco-friendly reaction medium, has been utilized for the first time in this reaction. The merits of the presented protocol include the high yields and catalyst reusability and the protocol precludes the use of metals and organic solvents. The present method is much milder but more advanced than those reported earlier.
- Kumar, Sumit,Verma, Nishant,Ahmed, Naseem
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p. 85128 - 85138
(2015/10/28)
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- Synthesis, antiviral bioactivity of novel 4-thioquinazoline derivatives containing chalcone moiety
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A series of novel 4-thioquinazoline derivatives containing chalcone moiety were designed, synthesized and systematically evaluated for their antiviral activity against TMV. The bioassay results showed that most of these compounds exhibited moderate to good anti-TMV activity. In particular, compounds M2 and M6 possessed appreciable protection activities against TMV in vivo, with 50% effective concentration (EC50) values of 138.1 and 154.8 μg/mL, respectively, which were superior to that of Ribavirin (436.0 μg/mL). The results indicated that chalcone derivatives containing 4-thioquinazoline moiety could effectively control TMV. Meanwhile, the structure-activity relationship (SAR) of the target compounds, studied using the three-dimensional quantitative structure-activity relationship (3D-QSAR) method of comparative molecular field analysis (CoMFA) based on the protection activities against TMV, demonstrated that the CoMFA model exhibited good predictive ability with the cross-validated q2 and non-cross-validated r2 values of 0.674 and 0.993, respectively. Meanwhile, the microscale thermophoresis (MST) experimental showed that the compound M6 may interaction with the tobacco mosaic virus coat protein (TMV CP).
- Wan, Zhihua,Hu, Deyu,Li, Pei,Xie, Dandan,Gan, Xiuhai
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supporting information
p. 11861 - 11874
(2015/08/18)
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