Akademik Veri Yönetim Sistemi
Journal of Biochemical and Molecular Toxicology, cilt.39, sa.9, 2025 (SCI-Expanded)
In this study, a novel series of multifunctional sulfonamide-based compounds (1–9) incorporating aziridine, dithiocarbamate, thiocyanate, and benzo[d]thiazole fragments were synthesized through nucleophilic substitution reactions using N-2,3-dichloropropylbenzenesulfonamide as the key intermediate. The chemical structures of the synthesized compounds were elucidated by spectroscopic techniques including ¹H NMR, ¹³C NMR, and elemental analysis. The inhibitory potentials of the synthesized compounds were assessed against three key enzymes: human carbonic anhydrase isoforms I and II (hCA I and hCA II) and acetylcholinesterase (AChE). Among the synthesized derivatives, compound 3 demonstrated the highest inhibitory effect against hCA I with an Ki of 49.45 ± 9.13 nM, exhibiting approximately 4.8-fold stronger inhibition than acetazolamide (AZA). Similarly, compound 9 was the most potent inhibitor of hCA II (Ki: 36.77 ± 8.21 nM), being 5.1-fold more effective than AZA. In the AChE inhibition assay, both compounds 3 and 2 showed superior activity over the reference drug tacrine (TAC), with Ki values of 148.67 ± 78.78 nM and 151.21 ± 11.78 nM, respectively, corresponding to 2.17-fold and 2.13-fold greater potency than TAC. The molecular docking studies were performed to examine the interactions between most potent compounds and proteins. These results emphasize the importance of present structural motifs for the various interactions. These findings support the rational design of multifunctional sulfonamides as promising scaffolds for the development of potent enzyme inhibitors targeting both CA and AChE-related pathologies.