2. Academic Validation
  3. Discovery and Synthesis of Novel Furan and Thiophene Sulfonamide-Based Derivatives as Dual-Functional α‑Glucosidase Inhibitors

Discovery and Synthesis of Novel Furan and Thiophene Sulfonamide-Based Derivatives as Dual-Functional α‑Glucosidase Inhibitors

  • ACS Med Chem Lett. 2026 Jan 20;17(2):464-475. doi: 10.1021/acsmedchemlett.5c00677.
Zeng Yi Fan 1,  Si Tu Xiong 2 3,  Song Hui Xu 2 3,  Li Ping Cheng 1
Affiliations

Affiliations

  • 1 Faculty of Chemical Engineering and Energy Technology, Shanghai Institute of Technology, Shanghai 201418, China.
  • 2 Department of Urology, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330031, Jiangxi, China.
  • 3 Jiangxi Provincial Key Laboratory of Urinary System Diseases, Nanchang 330006, Jiangxi, China.
PMID: 41704351 DOI: 10.1021/acsmedchemlett.5c00677
Abstract

Molecular docking and dynamics simulations identified sulfonamide lead compound 4a (ZINC818285131) as an α-glucosidase inhibitor. Subsequent structural modification yielded a novel series of furan/thiophene-containing sulfonamide derivatives (4b-4p). In vitro assays revealed potent α-glucosidase inhibition for compounds 4i, 4m, 4n, and 4p, with IC50 values ranging from 2.03 μM to 2.69 μM. Notably, 4i and 4p (IC50 = 2.03 ± 0.05 μM and 2.14 ± 0.01 μM, respectively) surpassed standard acarbose IC50 = 3.20 ± 0.22 μM. Molecular docking suggested enhanced activity for 4i and 4p stems from hydrogen bonding and hydrophobic interactions with the enzyme. All compounds complied with Lipinski's rule of five. Comprehensive ADMET profiling indicated favorable properties for the most potent derivative, 4i, which also exhibited promising antioxidant and Anticancer potential. These findings may advance the discovery of new therapies for type-2 diabetes and bladder Cancer.

Keywords

Diabetes mellitus; antioxidant; bladder cancer; molecular dynamics (MD) simulation; α-glucosidase inhibitor.

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