Triazinoindole analogs as potent inhibitors of α-glucosidase: synthesis, biological evaluation and molecular docking studies

Rahim F; Ullah K; Ullah H; Wadood A; Taha M; Ur Rehman A; uddin I; Ashraf M; Shaukat A; Rehman W; Hussain S; Khan KM

doi:10.1016/j.bioorg.2014.12.001

Triazinoindole analogs as potent inhibitors of α-glucosidase: synthesis, biological evaluation and molecular docking studies

Rahim F ¹ , Ullah K ² , Ullah H ² , Wadood A ³ , Taha M ⁴ , Ur Rehman A ³ Show all authors , uddin I ² , Ashraf M ⁵ , Shaukat A ⁵ , Rehman W ² , Hussain S ⁶ , Khan KM ⁶

Affiliations

¹ Department of Chemistry, Hazara University, Mansehra 21120, Khyber Pukhtunkhwa, Pakistan. Electronic address: fazalstar@gmail.com
² Department of Chemistry, Hazara University, Mansehra 21120, Khyber Pukhtunkhwa, Pakistan
³ Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University Mardan, Pakistan
⁴ Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), PuncakAlam Campus, 42300 Bandar PuncakAlam, Selangor DarulEhsan, Malaysia; Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia
⁵ Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan
⁶ H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan

Bioorg Chem, 2015 Feb;58:81-7.

PMID: 25528720 DOI: 10.1016/j.bioorg.2014.12.001

Abstract

A new series of triazinoindole analogs 1-11 were synthesized, characterized by EI-MS and (1)H NMR, evaluated for α-glucosidase inhibitory potential. All eleven (11) analogs showed different range of α-glucosidase inhibitory potential with IC50 value ranging between 2.46±0.008 and 312.79±0.06 μM when compared with the standard acarbose (IC50, 38.25±0.12 μM). Among the series, compounds 1, 3, 4, 5, 7, 8, and 11 showed excellent inhibitory potential with IC50 values 2.46±0.008, 37.78±0.05, 28.91±0.0, 38.12±0.04, 37.43±0.03, 36.89±0.06 and 37.11±0.05 μM respectively. All other compounds also showed good enzyme inhibition. The binding modes of these analogs were confirmed through molecular docking.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.