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Synthesis and in vitro carbonic anhydrases and acetylcholinesterase inhibitory activities of novel imidazolinone‐based benzenesulfonamides
Author(s) -
Tugrak Mehtap,
Gul Halise Inci,
Demir Yeliz,
Levent Serkan,
Gulcin Ilhami
Publication year - 2021
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.202000375
Subject(s) - chemistry , sulfanilamide , acetylcholinesterase , stereochemistry , carbonic anhydrase , sulfonamide , thiadiazoles , active site , moiety , enzyme , carbonic anhydrase i , sulfamerazine , nitro , sulfadiazine , medicinal chemistry , biochemistry , organic chemistry , antibiotics , alkyl
New imidazolinone‐based benzenesulfonamides 3a–e and 4a–e were synthesized in three steps and their chemical structures were confirmed by 1 H NMR (nuclear magnetic resonance), 13 C NMR, and high‐resolution mass spectrometry. The benzenesulfonamides used were sulfacetamide ( 3a , 4a ), sulfaguanidine ( 3b , 4b ), sulfanilamide ( 3c , 4c ), sulfadiazine ( 3d , 4d ), sulfamerazine ( 3e ), and sulfathiazole ( 4e ). The compounds were evaluated against carbonic anhydrase (CA) and acetylcholinesterase (AChE) enzymes to obtain possible drug candidate/s. The lead compounds of the series were 3a and 4a against human CA (hCA) I, whereas 3d and 4a were leads against hCA II in terms of K i values. Series 4 includes more effective CAs inhibitors than series 3 (except 3d ). Series 4 compounds having a nitro group (except 4d ) were 3.3–4.8 times more selective inhibitors than their corresponding analogues 3a–d in series 3 , in which hydrogen was located in place of the nitro group, by considering K i values against hCA II. Compounds 3c and 4c , where the sulfanilamide moiety is available, were the leads in terms of AChE inhibition with the lowest K i values. The use of secondary sulfonamides was a more effective modification on CA inhibition, whereas the primary sulfonamide was the effective substitution in terms of AChE inhibitory potency.