2026-10-19T01:18:07Zhttps://ebyu-rdlopen.rawdatalibrary.net/oai/request

oai:ebyu-rdlopen.rawdatalibrary.net:ebyu/110622026-10-18T21:13:16Zopenairedrivercom_ebyu_10000col_ebyu_10001

Dynamics of small molecule-enzyme interactions: Novel benzenesulfonamides as multi-target agents endowed with inhibitory effects against some metabolic enzymesGüleç, ÖzcanTürkeş, CüneytArslan, MustafaIşık, MesutDemir, YelizDuran, Hatice EsraFırat, MuhammetKüfrevioğlu, Ömer İrfanBeydemir, ŞükrüCarbonic anhydraseMolecular dockingOxadiazoleSulfonamideTirazoleα-amylaseα-glycosidasealpha-AmylasesBenzenesulfonamidesCarbonic Anhydrase ICarbonic Anhydrase IICarbonic Anhydrase InhibitorsHumansMolecular Docking SimulationStructure-Activity RelationshipSulfonamides4 [4 [[[5 (4 sulfamoylphenyl) 1,3,4 oxadiazol 2 yl]thio]methyl] 1h 1,2,3 triazol 1 yl]benzenesulfonamide4 [4 [[[5 (4 sulfamoylphenyl) 1,3,4 oxadiazol 2 yl]thio]methyl] 1h 1,2,3 triazol 1 yl]benzoic acid4 [5 [[(1 pentyl 1h 1,2,3 triazol 4 yl)methyl]thio] 1,3,4 oxadiazol 2 yl]benzenesulfonamide4 [5 [[(1 phenyl 1h 1,2,3 triazol 4 yl)methyl]thio] 1,3,4 oxadiazol 2 yl]benzenesulfonamide4 [5 [[[1 (2 chlorophenyl) 1h 1,2,3 triazol 4 yl]methyl]thio] 1,3,4 oxadiazol 2 yl]benzenesulfonamide4 [5 [[[1 (3 fluorophenyl) 1h 1,2,3 triazol 4 yl]methyl]thio] 1,3,4 oxadiazol 2 yl]benzenesulfonamide4 [5 [[[1 (4 bromophenyl) 1h 1,2,3 triazol 4 yl]methyl]thio] 1,3,4 oxadiazol 2 yl]benzenesulfonamide4 [5 [[[1 (4 chlorophenyl) 1h 1,2,3 triazol 4 yl]methyl]thio] 1,3,4 oxadiazol 2 yl]benzenesulfonamide4 [5 [[[1 (4 cyanophenyl) 1h 1,2,3 triazol 4 yl]methyl]thio) 1,3,4 oxadiazol 2 yl]benzenesulfonamide4 [5 [[[1 (4 fluorophenyl) 1h 1,2,3 triazol 4 yl]methyl]thio] 1,3,4 oxadiazol 2 yl]benzenesulfonamide4 [5 [[[1 (4 hydroxyphenyl) 1h 1,2,3 triazol 4 yl]methyl]thio] 1,3,4 oxadiazol 2 yl]benzenesulfonamide4 [5 [[[1 (4 iodophenyl) 1h 1,2,3 triazol 4 yl]methyl]thio] 1,3,4 oxadiazol 2 yl]benzenesulfonamide4 [5 [[[1 (5 chloro 2 nitrophenyl) 1h 1,2,3 triazol 4 yl]methyl]thio] 1,3,4 oxadiazol 2 yl]benzenesulfonamideacetazolamideIn contemporary medicinal chemistry, employing a singular small molecule to concurrently multi-target disparate molecular entities is emerging as a potent strategy in the ongoing battle against metabolic disease. In this study, we present the meticulous design, synthesis, and comprehensive biological evaluation of a novel series of 1,2,3-triazolylmethylthio-1,3,4-oxadiazolylbenzenesulfonamide derivatives (8a-m) as potential multi-target inhibitors against human carbonic anhydrase (EC.4.2.1.1, hCA I/II), α-glycosidase (EC.3.2.1.20, α-GLY), and α-amylase (EC.3.2.1.1, α-AMY). Each synthesized sulfonamide underwent rigorous assessment for inhibitory effects against four distinct enzymes, revealing varying degrees of hCA I/II, a-GLY, and a-AMY inhibition across the tested compounds. hCA I was notably susceptible to inhibition by all compounds, demonstrating remarkably low inhibition constants (KI) ranging from 42.20 ± 3.90 nM to 217.90 ± 11.81 nM compared to the reference standard AAZ (KI of 439.17 ± 9.30 nM). The evaluation against hCA II showed that most of the synthesized compounds exhibited potent inhibition effects with KI values spanning the nanomolar range 16.44 ± 1.53–70.82 ± 4.51 nM, while three specific compounds, namely 8a-b and 8d, showcased lower inhibitory potency than other derivatives that did not exceed that of the reference drug AAZ (with a KI of 98.28 ± 1.69 nM). Moreover, across the spectrum of synthesized compounds, potent inhibition profiles were observed against diabetes mellitus-associated α-GLY (KI values spanning from 0.54 ± 0.06 μM to 5.48 ± 0.50 μM), while significant inhibition effects were noted against α-AMY, with IC50 values ranging between 0.16 ± 0.04 μM and 7.81 ± 0.51 μM) compared to reference standard ACR (KI of 23.53 ± 2.72 μM and IC50 of 48.17 ± 2.34 μM, respectively). Subsequently, these inhibitors were evaluated for their DPPH· and ABTS+· radical scavenging activity. Moreover, molecular docking investigations were meticulously conducted within the active sites of hCA I/II, α-GLY, and α-AMY to provide comprehensive elucidation and rationale for the observed inhibitory outcomes. © 2024 Elsevier Inc.Academic Press Inc.2024Articlehttps://rdlopen.rawdatalibrary.net/r/ebyu/11062https://doi.org/10.1016/j.abb.2024.1100990003-9861enArchives of Biochemistry and Biophysicsinfo:eu-repo/semantics/openAccessinfo:eu-repo/semantics/articlehttps://ebyu-rdlopen.rawdatalibrary.net/tr/items/ebyu/11062