Synthesis, Biological Evaluation and Molecular Docking Study of Hydrazone-Containing Pyridinium Salts as Cholinesterase Inhibitors

WOS: 000382352700006PubMed ID: 27581632A series of pyridinium salts bearing alkylphenyl groups at 1 position and hydrazone structure at 4 position of the pyridinium ring were synthesized and evaluated for the inhibition of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. The cholinesterase (ChE) inhibitory activity studies were carried out by using the Ellman's colorimetric method. All compounds displayed considerable AChE and BuChE inhibitory activity and some of the compounds manifested remarkable anti-AChE activity compared to the reference compound, galantamine. Among the title compounds, the series including benzofuran aromatic ring exhibited the best inhibitory activity both on AChE and BuChE enzymes. Compound 3b, 4-[2-(1-(benzofuran-2-yl)ethylidene)hydrazinyl]-1-(3-Phenylpropyl)pyridinium bromide, was the most active compound with IC50 value of 0.23 (0.24) mu m against enantiomeric excess (ee)AChE (human (h)AChE) while compound 3a, 4-[2-(1-(benzofuran-2-yl)ethylidene)hydrazinyl]-1-phenethylpyridinium bromide, was the most active compound with IC50 value of 0.95 mu m against BuChE. Moreover, 3a and b exhibited higher activity than the reference compound galantamine (eeAChE (hAChE) IC50 0.43 (0.52) mu m; BuChE IC50 14.92 mu m). Molecular docking studies were carried out on 3b having highest inhibitory activity against AChE.Research Grants from Ege University [13/Ecz/026]This study was supported by Research Grants from Ege University (Project Number: 13/Ecz/026). The authors would like to thank the Pharmaceutical Sciences Research Centre (FABAL) at Ege University Faculty of Pharmacy for spectral analyses of the compounds

Synthesis, biological activity and molecular modeling studies on 1H-benzimidazole derivatives as acetylcholinesterase inhibitors

WOS: 000323294600007PubMed ID: 23891231A series of N-(2-[4-(1H-benzimidazole-2-yl)phenoxy]ethyl}substituted amine derivatives were designed to assess cholinesterase inhibitor activities. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitor activities were evaluated in vitro by using Ellman's method. It was discovered that most of the compounds displayed AChE and/or BuChE inhibitor activity and few compounds were selective against AChE/BuChE. Compound 3c and 3e were the most active compounds in the series against eeAChE and hAChE, respectively. Molecular docking studies and molecular dynamics simulations were also carried out. (C) 2013 Elsevier Ltd. All rights reserved

Synthesis and molecular docking studies of some 4-phthalimidobenzenesulfonamide derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors

A series of 4-phthalimidobenzenesulfonamide derivatives were designed, synthesized and evaluated for the inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Structures of the title compounds were confirmed by spectral and elemental analyses. The cholinesterase (ChE) inhibitory activity studies were carried out using Ellman’s colorimetric method. The biological activity results revealed that all of the title compounds (except for compound 8) displayed high selectivity against AChE. Among the tested compounds, compound 7 was found to be the most potent against AChE (IC50= 1.35 ± 0.08 μM), while compound 3 exhibited the highest inhibition against BuChE (IC50= 13.41 ± 0.62 μM). Molecular docking studies of the most active compound 7 in AChE showed that this compound can interact with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE

Synthesis and cytotoxic activity of some 2-(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)acetamide derivatives

WOS: 000317819800004Isatin, 1H-indoline-2,3-dione, an endogenous compound, is also a synthetically versatile molecule that possesses a diversity of biological activities including anticonvulsant, antibacterial, antifungal, antiviral, anticancer, and cytotoxic properties. Based on the promising cytotoxic activity studies on N-substituted isatin derivatives, a series of 18 derivatives of 2-(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)-N-phenylacetamide were designed, synthesized, and characterized according to their analytical and spectral data. All of the compounds were evaluated for their cytotoxic activity against MCF7, A549, HeLa, and HEK293 cell lines by real time cell analyzer. Etoposide was used as a standard compound. Briefly, ortho substitutions gave better results compared to meta and para substitutions on the N-phenyl ring and compounds bearing ortho substitutions were more effective on MCF7 cell lines than A549 and HeLa cell lines. 2-(2,3-Dioxo-2,3-dihydro-1H-indol-1-yl)-N-(2-isopropylphenyl)acetamide was the most active compound against all the tested cell lines.Ege UniversityEge University [09/ECZ/036]This study was supported by a research grant from Ege University (Project number: 09/ECZ/036). We thank the Pharmaceutical Sciences Research Center (FABAL) of the Faculty of Pharmacy, Ege University, for support with the equipment

Synthesis, bioactivity and molecular modeling studies on potential anti-Alzheimer piperidinehydrazide-hydrazones

WOS: 000469026400086PubMed ID: 30538051A group of N-benzylpiperidine-3/4-carbohydrazide-hydrazones were designed, synthesized and evaluated for acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) activities, A beta(42) self-aggregation inhibitory potentials, and antioxidant capacities, in vitro. All of the compounds displayed eeAChE and huAChE inhibitory activity in a range of IC50 = 5.68-11.35 mu M and IC50 = 8.80-74.40 mu M, respectively and most of the compounds exhibited good to moderate inhibitory activity on BuChE enzyme. Kinetic analysis and molecular modeling studies were also performed for the most potent compounds (1g and 1j). Not only the molecular modeling studies but also the kinetic analysis suggested that these compounds might be able to interact with the catalytic active site (CAS) and the peripheral anionic site (PAS) of the enzymes. In the light of the results, compound 1g and compound 1j may be suggested as lead compounds for multifunctional therapy of AD.TUBITAK (The Scientific and Technological Research Council of Turkey)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [214S083]This project was supported by TUBITAK (The Scientific and Technological Research Council of Turkey), Project Number: 214S083

1H-benzimidazole derivatives as butyrylcholinesterase inhibitors: synthesis and molecular modeling studies

WOS: 000385175500024A series of N-{2-[2-(1H-benzimidazole-2-yl)phenoxy]ethyl} substituted amine derivatives were synthesized and tested for their cholinesterase inhibitor activity. Acetylcholinesterase and butyrylcholinesterase inhibitor activities were evaluated in vitro by using Ellman's method. According to the activity results, all of the compounds displayed moderate acetylcholinesterase inhibitory activity and most of the compounds displayed remarkable butyrylcholinesterase inhibitory activity. Compound 3d was the most active compound in the series and also a selective butyrylcholinesterase inhibitor. Molecular docking studies and molecular dynamic simulations were also carried out.TUBITAK (Turkish Scientific and Technical Research Council)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [213S027]This study was partially supported by TUBITAK (Turkish Scientific and Technical Research Council) (Project number: 213S027). We appreciate the support of Professor Dr. Wolfgang Sippl for molecular modeling studies. We also thank the Medicinal Chemistry Department of Martin Luther University Institute of Pharmacy and also Pharmaceutical Sciences Research Centre (FABAL) of Ege University Faculty of Pharmacy for equipmental support