Synthesis and in vitro carbonic anhydrases and acetylcholinesterase inhibitory activities of novel imidazolinone‐based benzenesulfonamides

• Published in: Archiv der Pharmazie (Weinheim) 2021-04, Vol.354 (4), p.e2000375-n/a
• Main Authors: Tugrak, Mehtap, Gul, Halise Inci, Demir, Yeliz, Levent, Serkan, Gulcin, Ilhami
• Format: Article
• Language: English
• Subjects: acetylcholinesterase; Acetylcholinesterase - metabolism; benzenesulfonamide; Benzenesulfonamides; carbonic anhydrase; Carbonic Anhydrase Inhibitors - chemical synthesis; Carbonic Anhydrase Inhibitors - chemistry; Carbonic Anhydrase Inhibitors - pharmacology; Carbonic Anhydrases - metabolism; Cholinesterase Inhibitors - chemical synthesis; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Humans; Imidazolines - chemistry; Imidazolines - pharmacology; imidazolinone; Molecular Structure; NMR; Nuclear magnetic resonance; Sulfonamides - chemical synthesis; Sulfonamides - chemistry; Sulfonamides - pharmacology; synthesis
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.202000375

New imidazolinone‐based benzenesulfonamides 3a–e and 4a–e were synthesized in three steps and their chemical structures were confirmed by 1H NMR (nuclear magnetic resonance), 13C 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 Ki 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 Ki 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 Ki 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. New imidazolinone‐based benzenesulfonamides (3a–e and 4a–e) were synthesized and evaluated for their activities against human carbonic anhydrase isoenzymes I and II (hCA I/II) and acetylcholinesterase (AChE). The use of secondary sulfonamides was a more effective modification on hCA inhibition, whereas the primary sulfonamide was the effective substitution in terms of AChE inhibitory potency.