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Synthesis, biological evaluation, and docking studies of some 5‐chloro‐2(3 H )‐benzoxazolone Mannich bases derivatives as cholinesterase inhibitors
Author(s) -
Uysal Sirin,
Parlar Sulunay,
Tarikogullari Ayse H.,
Aydin Kose Fadime,
Alptuzun Vildan,
Soyer Zeynep
Publication year - 2018
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201700273
Subject(s) - docking (animal) , chemistry , cholinesterase , stereochemistry , combinatorial chemistry , organic chemistry , pharmacology , biology , medicine , nursing
A series of N ‐substituted‐5‐chloro‐2(3 H )‐benzoxazolone derivatives were synthesized and evaluated for their acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) inhibitory, and antioxidant activities. The 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 free radical scavenging activity was also determined by in vitro ABTS (2,2‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid)) assay. The biological activity results revealed that all of the title compounds displayed higher AChE inhibitory activity than the reference compound, rivastigmine, and were selective for AChE. Among the tested compounds, compound 7 exhibited the highest inhibition against AChE (IC 50 = 7.53 ± 0.17 μM), while compound 11 was found to be the most active compound against BuChE (IC 50 = 17.50 ± 0.29 μM). The molecular docking study of compound 7 showed that this compound can interact with the catalytic active site (CAS) of AChE and also has potential metal chelating ability and a proper log P value. On the other hand, compound 2 bearing a methyl substituent at the ortho position on the phenyl ring showed better radical scavenging activity (IC 50 = 1.04 ± 0.04 mM) than Trolox (IC 50 = 1.50 ± 0.05 mM).