- Anti-melanogenesis and anti-tyrosinase properties of aryl-substituted acetamides of phenoxy methyl triazole conjugated with thiosemicarbazide: Design, synthesis and biological evaluations
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A series of aryl phenoxy methyl triazole conjugated with thiosemicarbazides were designed, synthesized, and evaluated for their tyrosinase inhibitory activities in the presence of L-dopa and L-tyrosine as substrates. All the compounds showed tyrosinase inhibition in the sub-micromolar concentration. Among the derivatives, compound 9j bearing benzyl displayed exceptionally high potency against tyrosinase with IC50 value of 0.11 μM and 0.17 μM in the presence of L-tyrosine and L-dopa as substrates which is significantly lower than that of kojic acid as the positive control with an IC50 value of 9.28 μM for L-tyrosine and 9.30 μM for L-dopa. According to Lineweaver–Burk plot, 9j demonstrated an uncompetitive type of inhibition in the kinetic assay. Also, in vitro antioxidant activities determined by DPPH assay recorded an IC50 value of 68.43 μM for 9i. The melanin content of 9j was determined on B16F10 melanoma human cells which demonstrated a significant reduction of the melanin content. Moreover, the binding energies corresponding to the same ligand as well as computer-aided drug-likeness and pharmacokinetic studies were also carried out. Compound 9j also possessed metal chelation potential correlated to its high anti-TYR activity.
- Hosseinpoor, Hona,Moghadam Farid, Sara,Iraji, Aida,Askari, Sadegh,Edraki, Najmeh,Hosseini, Samanesadat,Jamshidzadeh, Akram,Larijani, Bagher,Attarroshan, Mahshid,Pirhadi, Somayeh,Mahdavi, Mohammad,Khoshneviszadeh, Mehdi
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- Novel (thio)barbituric-phenoxy-N-phenylacetamide derivatives as potent urease inhibitors: synthesis, in vitro urease inhibition, and in silico evaluations
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A novel series of (thio)barbituric-phenoxy-N-phenylacetamide derivatives 7a-l was synthesized and evaluated against Helicobacter pylori urease. The latter assay revealed that all the synthesized compounds 7a-l (IC50 = 0.69 ± 0.33–2.47 ± 0.23?μM
- Sedaghati, Saeb,Azizian, Homa,Montazer, Mohammad Nazari,Mohammadi-Khanaposhtani, Maryam,Asadi, Mehdi,Moradkhani, Fatemeh,Ardestani, Mehdi Shafiee,Asgari, Mohammad Sadegh,Yahya-Meymandi, Azadeh,Biglar, Mahmood,Larijani, Bagher,Sadat-Ebrahimi, Seyed Esmaeil,Foroumadi, Alireza,Amanlou, Massoud,Mahdavi, Mohammad
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- α-Glucosidase and α-amylase inhibition, molecular modeling and pharmacokinetic studies of new quinazolinone-1,2,3-triazole-acetamide derivatives
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In this study, a new series of quinazolinone-1,2,3-triazole-acetamide hybrids 8a–m, using by molecular hybridization of the potent α-glucosidase inhibitor pharmacophores, was designed and evaluated against carbohydrate-hydrolyzing enzymes α-glucosidase and α-amylase. All the synthesized compounds with IC50 values in the range of 45.3 ± 1.4 μM to 195.5 ± 4.7 μM were significantly more potent than standard inhibitor against α-glucosidase, while these compounds were not active against α-amylase in comparison to standard inhibitor. Representatively, compound 8a with IC50 = 45.3 ± 1.4 μM was around 17 times more potent than standard inhibitor acarbose (IC50 = 750.0 ± 12.5 μM). The inhibition kinetic analysis of the compound 8a indicated that this compound was a competitive α-glucosidase inhibitor. Molecular modeling analysis confirmed that the most potent inhibitors 8a and 8b well accommodated in the modeled α-glucosidase active site and it was also revealed that these compounds formed stable inhibitor–receptor complexes with the α-glucosidase in comparison to acarbose. In silico pharmacokinetic and toxicity of the most potent compounds were evaluated and obtained results were compared with acarbose. Furthermore, the most potent compounds were also evaluated against human normal cells and no cytotoxicity was observed.
- Yavari, Ali,Mohammadi-Khanaposhtani, Maryam,Moradi, Shahram,Bahadorikhalili, Saeed,Pourbagher, Roghayeh,Jafari, Nasrin,Faramarzi, Mohammad Ali,Zabihi, Ebrahim,Mahdavi, Mohammad,Biglar, Mahmood,Larijani, Bagher,Hamedifar, Haleh,Hajimiri, Mir Hamed
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p. 702 - 711
(2021/01/18)
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- New 4,5-diphenylimidazole-acetamide-1,2,3-triazole hybrids as potent α-glucosidase inhibitors: synthesis, in vitro and in silico enzymatic and toxicity evaluations
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Herein, a new series of 4,5-diphenylimidazole-acetamide-1,2,3-triazole hybrids as potent α-glucosidase inhibitors was designed and synthesized. All the synthesized compounds exhibited excellent inhibition potencies (IC50 values = 55.6–149.2 μM)
- Sepehri, Nima,Azizian, Homa,Ghadimi, Reza,Abedinifar, Fahimeh,Mojtabavi, Somayeh,Faramarzi, Mohammad Ali,Moghadamnia, Ali Akbar,Zabihi, Ebrahim,Mohebbi, Gholamhossein,Larijani, Bagher,Hamedifar, Haleh,Mohammadi-Khanaposhtani, Maryam,Mahdavi, Mohammad
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p. 679 - 693
(2021/06/14)
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- Synthesis and antimicrobial evaluations of sulfur inserted fluoro-benzimidazoles
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A new series of fluorinated sulfur inserted benzimidazole analogues Za-i were synthesized and characterized. The new compounds were screened for their antimicrobial and antioxidant potential. The synthesized compounds were obtained by multiple step synthesis, initiating from the synthesis of 5-(difluoromethoxy)-1H-benzimidazole-2-thiol X. The compounds Ya-i prepared by reacting differently substituted anilines with chloroacetylchloride and triethylamine in DMF. Finally, the compound X was reacted with different derivatives of 2-chloro-N-phenylacetamide resulting in formation of titled compounds Za-i. The synthesized compounds (Za-Zi) were characterized by spectral analysis viz.1H & 13C NMR, mass spectra, elemental analysis and IR. The in vitro antimicrobial potential against Gram-positive (S. aureus and E. faecalis) and Gram-negative bacterial (E. coli and P.aeruginosa) strains as well as fungi (A. niger and C. albicans) was recorded for the obtained compounds. Some of the compounds exhibited encouraging results (in MIC) against Gram-positive and Gram-negative bacterial strains. These studies thus suggest that the designed sulfur inserted fluoro-benzimidazoles scaffold may serve as new promising template for further amplification as antimicrobial agents.
- Dwivedi, Parmesh Kumar,Chaturvedi, Devdutt
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p. 1525 - 1529
(2021/07/02)
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- Design, synthesis, and α-glucosidase-inhibitory activity of phenoxy-biscoumarin–N-phenylacetamide hybrids
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Thirteen new phenoxy-biscoumarin–N-phenylacetamide derivatives (7a–m) were designed based on a molecular hybridization approach as new α-glucosidase inhibitors. These compounds were synthesized with high yields and evaluated in vitro for their inhibitory activity against yeast α-glucosidase. The obtained results revealed that a significant proportion of the synthesized compounds showed considerable α-glucosidase-inhibitory activity in comparison to acarbose as a positive control. Representatively, 2-(4-(bis(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl)phenoxy)-N-(4-bromophenyl)acetamide (7f), with IC50 = 41.73 ± 0.38 μM against α-glucosidase, was around 18 times more potent than acarbose (IC50 = 750.0 ± 10.0 μM). This compound was a competitive α-glucosidase inhibitor. Molecular modeling and dynamic simulation of these compounds confirmed the obtained results through in vitro experiments. Prediction of the druglikeness/ADME/toxicity of the compound 7f and comparison with the standard drug acarbose showed that the new compound 7f was probably better than the standard drug in terms of toxicity.
- Ansari, Samira,Azizian, Homa,Pedrood, Keyvan,Yavari, Ali,Mojtabavi, Somayeh,Faramarzi, Mohammad A.,Golshani, Shiva,Hosseini, Samanesadat,Biglar, Mahmood,Larijani, Bagher,Rastegar, Hossein,Hamedifar, Haleh,Mohammadi-Khanaposhtani, Maryam,Mahdavi, Mohammad
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- 4-Oxobenzo[d]1,2,3-triazin-pyridinium-phenylacetamide derivatives as new anti-Alzheimer agents: design, synthesis, in vitro evaluation, molecular modeling, and molecular dynamic study
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A new series of 4-oxobenzo[d]1,2,3-triazin-pyridinium-phenylacetamide hybrids 8a–p was designed, synthesized, and screened as the potential cholinesterase inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Obtained anti-chol
- Hosseini, Fahimeh,Mohammadi-Khanaposhtani, Maryam,Azizian, Homa,Ramazani, Ali,Tehrani, Maliheh Barazandeh,Nadri, Hamid,Larijani, Bagher,Biglar, Mahmoud,Adibi, Hossein,Mahdavi, Mohammad
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p. 999 - 1012
(2020/01/11)
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- Synthesis and biological evaluation of new benzimidazole-1,2,3-triazole hybrids as potential α-glucosidase inhibitors
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In this study, a series of benzimidazole-1,2,3-triazole hybrids 8a-n as new α-glucosidase inhibitors were designed and synthesized. In vitro α-glucosidase inhibition activity results indicated that all the synthesized compounds (IC50 values ranging from 25.2 ± 0.9 to 176.5 ± 6.7 μM) exhibited more inhibitory activity in comparison to standard drug acarbose (IC50 = 750.0 ± 12.5 μM). Enzyme kinetic study on the most potent compound 8c revealed that this compound was a competitive inhibitor into α-glucosidase. Moreover, the docking study was performed in order to evaluation of interaction modes of the synthesized compounds in the active site of α-glucosidase and to explain structure-activity relationships of the most potent compounds and their corresponding analogs.
- Asadi, Mehdi,Asemanipoor, Nafise,Biglar, Mahmood,Faramarzi, Mohammad Ali,Hajimiri, Mir Hamed,Hamedifar, Haleh,Larijani, Bagher,Mahdavi, Mohammad,Mohammadi-Khanaposhtani, Maryam,Moradi, Shahram,Vahidi, Mahbobeh
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- Synthesis, characterization, molecular docking, and biological activities of coumarin–1,2,3-triazole-acetamide hybrid derivatives
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Coumarins and their derivatives are receiving increasing attention due to numerous biochemical and pharmacological applications. In this study, a series of novel coumarin–1,2,3-triazole-acetamide hybrids was tested against some metabolic enzymes including α-glycosidase (α-Gly), α-amylase (α-Amy), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), human carbonic anhydrase I (hCA I), and hCA II. The new coumarin–1,2,3-triazole-acetamide hybrids showed Ki values in the range of 483.50–1,243.04 nM against hCA I, 508.55–1,284.36 nM against hCA II, 24.85–132.85 nM against AChE, 27.17–1,104.36 nM against BChE,?590.42–1,104.36 nM against α-Gly,?and 55.38–128.63 nM against α-Amy. The novel coumarin–1,2,3-triazole-acetamide hybrids had effective inhibition profiles against all tested metabolic enzymes. Also, due to the enzyme inhibitory effects of the new hybrids, they are potential drug candidates to treat diseases such as epilepsy, glaucoma, type-2 diabetes mellitus (T2DM), Alzheimer's disease (AD), and leukemia. Additionally, these inhibition effects were compared with standard enzyme inhibitors like acetazolamide (for hCA I and II), tacrine (for AChE and BChE), and acarbose (for α-Gly and α-Amy). Also, those coumarin–1,2,3-triazole-acetamide hybrids with the best inhibition score were docked into the active site of the indicated metabolic enzymes.
- Sepehri, Nima,Mohammadi-Khanaposhtani, Maryam,Asemanipoor, Nafise,Hosseini, Samanesadat,Biglar, Mahmood,Larijani, Bagher,Mahdavi, Mohammad,Hamedifar, Haleh,Taslimi, Parham,Sadeghian, Nastaran,Gulcin, Ilhami
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- Structural Exploration of Quinazolin-4(3H)-ones as Anticonvulsants: Rational Design, Synthesis, Pharmacological Evaluation, and Molecular Docking Studies
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Anticonvulsants effective against multiple seizures are of wide interest as antiepileptic drugs, especially if active against pharmaco-resistant seizures. Herein, we synthesized 16 different, rationally designed 2-((6,7-dimethoxy-4-oxo-2-phenylquinazolin-3(4H)-yl)amino)-N-(substituted phenyl)acetamides and screened for anticonvulsant activities through in vivo experiments. Compound 4d emerged as prototype with excellent anti-seizure action in mice against electroshock, chemically induced and pharmaco-resistant 6-Hz seizure models with no symptoms of neurotoxicity and hepatotoxicity (ED50 = 23.5 mg/kg, MES, mice, i.p.; ED50 = 32.6 mg/kg, scPTZ, mice, i.p.; ED50 = 45.2 mg/kg, 6-Hz, mice, i.p.; TD50 = 325.9 mg/kg, mice, i.p.). In addition, investigation of compound 4l in mice for its pharmacological profile proved it as safer anticonvulsant, devoid of the side effects such as motor dysfunction and hepatotoxicity of classical antiepileptic drugs (ED50 = 26.1 mg/kg, MES, mice, i.p.; ED50 = 79.4 mg/kg, scPTZ, mice, i.p.; TD50 = 361.2 mg/kg, mice, i.p.). We also predicted physiochemical and pharmacokinetic properties of structurally optimized quinazolin-4(3H)-ones by a computational protocol. A combination of in vivo anticonvulsant profile, ex vivo toxicity, and in silico studies suggested that the synthesized compounds may be useful as broad-spectrum anti-seizure drug candidates with favorable pharmacokinetic parameters.
- Ugale, Vinod G.,Bari, Sanjay B.
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p. 864 - 880
(2016/11/09)
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- SPIRO-SUBSTITUTED OXINDOLE DERIVATIVES HAVING AMPK ACTIVITY
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The present invention relates to compounds of formula (I), which have valuable pharmacological properties, in particular are activators of AMPK and which are therefore useful in the treatment of certain disorders that can be prevented or treated by activation of this receptor. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2.
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Page/Page column 159; 160
(2015/01/07)
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- Synthesis, characterization and antimicrobial activity of 2-(11-oxodibenzo [b,f][1,4]thiazepin-10(11H)-yl)-N (substituted phenyl) acetamide derivatives
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Substituted dibenzo [b,f][1,4]thiazepines analogues carrying 2-chloro N-phenylacetamide moiety attached to 11-C position have been synthesized and evaluated using IR, 1H NMR and mass spectra. Antibacterial properties have been examined for the synthesized derivatives against gram positive and gram negative bacteria. 2-(11-Oxodibenzo [b,f][1,4]thiazepin-10(11H)-yl)-N phenylacetamide derivatives show good significant antimicrobial activity.
- Tailor, Jitesh H.,Patel, Priti C.,Malik
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p. 1263 - 1268
(2014/12/10)
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- Design, synthesis and neuropharmacological activity of dihydro imidazole derivatives
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A new series of dihydro imidazole derivatives have been synthesized and characterized by UV-Vis, IR, 'H NMR and mass spectroscopy. The synthesized compounds have been screened for neuro pharmacological activities. All the compounds are effective; amongst
- Mariappan,Alam, Sadrul,Sulharson,Haldar,Nath, Shyamalendu
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p. 568 - 572
(2013/06/26)
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- Tri-substituted triazoles as potent non-nucleoside inhibitors of the HIV-1 reverse transcriptase
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A new series of 1,2,4-triazoles was synthesized and tested against several NNRTI-resistant HIV-1 isolates. Several of these compounds exhibited potent antiviral activities against efavirenz- and nevirapine-resistant viruses, containing K103N and/or Y181C mutations or Y188L mutation. Triazoles were first synthesized from commercially available substituted phenylthiosemicarbazides, then from isothiocyanates, and later by condensing the desired substituted anilines with thiosemicarbazones.
- De La Rosa, Martha,Kim, Hong Woo,Gunic, Esmir,Jenket, Cheryl,Boyle, Uyen,Koh, Yung-hyo,Korboukh, Ilia,Allan, Matthew,Zhang, Weijian,Chen, Huanming,Xu, Wen,Nilar, Shahul,Yao, Nanhua,Hamatake, Robert,Lang, Stanley A.,Hong, Zhi,Zhang, Zhijun,Girardet, Jean-Luc
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p. 4444 - 4449
(2007/10/03)
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- Infrared and Raman spectra of substituted N-(phenyl)-2-chloroacetamides, XYC5-yNHCOCH2Cl (X = H, o/m/p-CH3, Cl or No2 and y = 1, 2 or 3)
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Several substituted N-(phenyl)-2-chloroacetamides of the configuration XyC6H5-yNHCOCH2Cl (where X = H, o/m/p-CH3, Cl or NO2 and y = 1, 2 or 3) have been synthesized, and their infrared and Raman spectra measured in the solid state with the objective of correlating CO and NH frequencies of these substituted phenylchloroacetamides with 35C1 NQR frequencies of the compounds. The study reveals that there is no systematic variation on substitution with either the infrared CO or NH absorption frequencies or the Raman scattered CO or NH frequencies. The effect of substitution in the phenyl ring in terms of either the electron-donating or electron-withdrawing groups could not be generalized. The same trend is observed even with the disubstituted phenyl-2-chloroacetamides, which may be due to the varying crystalline states of the amides on substitution, as the spectra are measured in the solid state. The infrared frequencies of the amides of the configuration XyC 6H5-yNHCOCH3 (where X = H, Cl, NO2 or CH3 and y = 1, 2 or 3) or CH3CONHR (where R = H, CH3, phenyl or substituted phenyl group) and RCONH2 (where R = H, CH3, C2H5, (CH3) 2, C6H5, (C6H5) 2, C6H5CH2, CH2Cl, CH2F, CHF2, CHCl2, CCl3) have also been examined for comparison purpose. The entire data indicate that even the spectra of these compounds do not show regular trends, for the reasons stated above. The correlation of CO and NH absorption frequencies with 35Cl NQR frequencies of the title compounds are also poor.
- Bhat, D. Krishna,Gowda, B. Thimme
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p. 163 - 168
(2007/10/03)
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- Activities of 2-carboxanilido 3-hydroxybenzo[b]thiophens against molluscs Biomphalaria
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The title compounds are shown to be nearly as active against molluscs as Niclosamide when they are either dihalogenated or monohalogenated and mononitrated on the benzene ring.
- Gayral,Buisson,Royer
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p. 187 - 189
(2007/10/02)
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