Synthesis and pharmacological effects of novel benzenesulfonamides carrying benzamide moiety as carbonic anhydrase and acetylcholinesterase inhibitors

Abstract

N -(1-(4-Methoxyphenyl)-3-oxo-3-((4-( N -(substituted)sulfamoyl)phenyl)amino)prop-1-en-1-yl)benzamides 3a – g were designed since sulfonamide and benzamide pharmacophores draw great attention in novel drug design due to their wide range of bioactivities including acetylcholinesterase (AChE) and human carbonic anhydrase I and II (hCA I and hCA II) inhibitory potencies. Structure elucidation of the compounds was carried out by 1H NMR, 13C NMR, and HRMS spectra. In vitro enzyme assays showed that the compounds had significant inhibitory potential against hCA I, hCA II, and AChE enzymes at nanomolar levels. Ki values were in the range of 4.07 ± 0.38 – 29.70 ± 3.18 nM for hCA I and 10.68 ± 0.98 – 37.16 ± 7.55 nM for hCA II while Ki values for AChE were in the range of 8.91 ± 1.65 – 34.02 ± 5.90 nM. The most potent inhibitors 3g (Ki = 4.07 ± 0.38 nM, hCA I), 3c (Ki = 10.68 ± 0.98 nM, hCA II ) , and 3f (Ki = 8.91 ± 1.65 nM, AChE) can be considered as lead compounds of this study with their promising bioactivity results. Secondary sulfonamides showed promising enzyme inhibitory effects on AChE while primary sulfonamide derivative was generally effective on hCA I and hCA II isoenzymes.

Synthesis of hydroxy benzoin/benzil analogs and investigation of their antioxidant, antimicrobial, enzyme inhibition, and cytotoxic activities

“…Acetylcholinesterase [55], butyrylcholine esterase [55], tyrosinase [56], α-amylase [58], α-glucosidase inhibition [58] activity results were made according to spectrophotometric methods. IC 50 values were calculated and given in Table 4.…”

“…Sample and blank absorbances were read after 10 min of incubation at 25 °C at 405 nm. Acetylcholinesterase inhibitory activity was given equivalent to galantamine [55], and the results were given in Table 4.…”

4‐Sulfamoylphenylalkylamides as Inhibitors of Carbonic Anhydrases Expressed in Vibrio cholerae

“…The experimental properties for 17–19, 25–30 and 33–35 matched with those reported in literature. [ 26 , 27 , 28 , 29 , 30 , 31 , 32 ]…”

Design, Synthesis, Characterization and Biological Activities of Novel S‐(Acyloxy)butyl‐N,N‐Diethyldithiocarbamate Compounds

“…Because of this role, α-glucosidase has been proposed as a potential therapeutic target for the treatment of type-2 diabetes in people. [14,15] In the literature, it is observed that many newly synthesized organic compounds including isatin mannich bases, [16] tetrahydropyrimidine-5-carboxylates, [17] diaryl ethers, [18] 4,5-disubstituted-2-thioxo-1,2,3,4-tetrahydropyrimidines, [19] bromophenols, [20] cyclic thioureas, [21] sulfamides derived from βbenzylphenethylamines, [22] new amides and thiazolidineones synthesized on an acetophenone base, [23] aminomethyl and alkoxymethyl derivatives, [24] 2-hydroxyethyl substituted NHC precursors, [25] phloroglucinol derivatives, [26] novel N,N'-biscyanomethylamine and alkoxymethylamine derivatives, [27] Meta-cyanobenzyl substituted benzimidazoles, [28] novel amides of 1,1-bis-(carboxymethylthio)-1-arylethanes, [29] novel trischalcones, [30] imidazole derivatives, bis-sulfone derivatives, [31] novel benzo[b]xanthene derivatives, [32] nitrogen, phosphorus, selenium and sulfur-containing heterocyclic compounds, [33] Schiff bases containing phenol ring, [34] and piperazine derivatives [35] effectively inhibit AChE and BChE enzymes. All of these newly synthesized molecules, which inhibit both cholinergic enzymes, contain many functional groups that are important for biological activity.…”