| Yazarlar (9) |
Özcan Güleç
|
|
Cüneyt Türkeş
Erzincan Binali Yıldırım Üniversitesi, Türkiye |
|
Mustafa Arslan
Türkiye |
|
Mesut Işık
Bilecik Şeyh Edebali Üniversitesi, Türkiye |
|
Yeliz Demir
Ardahan Üniversitesi, Türkiye |
Doç. Dr. Hatice Esra DURAN
Kafkas Üniversitesi, Türkiye |
|
Muhammet Fırat
|
|
Ömer İrfan Küfrevioğlu
Atatürk Üniversitesi, Türkiye |
|
Şükrü Beydemir
Anadolu Üniversitesi, Türkiye |
| Özet |
| In 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 (K) ranging from 42.20 ± 3.90 nM to 217.90 ± 11.81 nM compared to the reference standard AAZ (K of 439.17 ± 9.30 nM). The evaluation against hCA II showed that most of the synthesized compounds exhibited potent inhibition effects with K 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 K of 98.28 ± 1.69 nM). Moreover, across the spectrum of synthesized compounds, potent inhibition profiles were observed against diabetes mellitus-associated α-GLY (K values spanning from 0.54 ± 0.06 μM to 5.48 ± 0.50 μM), while significant inhibition effects were noted against α-AMY, with IC values ranging between 0.16 ± 0.04 μM and 7.81 ± 0.51 μM) compared to reference standard ACR (K of 23.53 ± 2.72 μM and IC 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. |
| Anahtar Kelimeler |
| Carbonic anhydrase | alpha-glycosidase | alpha-amylase | Sulfonamide | Tirazole | Oxadiazole | Molecular docking |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale |
| Dergi Adı | Archives of Biochemistry and Biophysics |
| Dergi ISSN | 0003-9861 Wos Dergi Scopus Dergi |
| Dergi Tarandığı Indeksler | SCI-Expanded |
| Dergi Grubu | Q2 |
| Makale Dili | İngilizce |
| Basım Tarihi | 09-2024 |
| Cilt No | 759 |
| Doi Numarası | 10.1016/j.abb.2024.110099 |
| Makale Linki | https://doi.org/10.1016/j.abb.2024.110099 |
| Atıf Sayıları | |
| WoS | 23 |
| Google Scholar | 26 |
