Affiliations 

  • 1 Department of Chemistry, Hazara University, Mansehra 21120, Pakistan
  • 2 Department of Chemistry, Hazara University, Mansehra 21120, Pakistan. Electronic address: fazalstar@gmail.com
  • 3 Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia. Electronic address: mtaha@iau.edu.sa
  • 4 Department of Chemistry, University of Poonch, Rawalakot, AJK, Pakistan
  • 5 Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan
  • 6 Faculty of Pharmacy, Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, Bandar Puncak Alam, Selangor 42300, Malaysia; Atta-ur-Rahman Institute for Natural Product Discovery (AuRIns), Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, Bandar Puncak Alam, Selangor 42300, Malaysia
  • 7 Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Ad Diriyah 13713, Saudi Arabia
  • 8 Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
  • 9 Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
  • 10 H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Int J Biol Macromol, 2022 Feb 28;199:77-85.
PMID: 34968547 DOI: 10.1016/j.ijbiomac.2021.12.147

Abstract

Triazinoindole bearing thiadiazole derivatives (1-25) have been synthesized and characterized through different spectroscopic techniques such as 1H, 13C-NMR and HREI-MS. The purpose of the study was to investigate the anti-diabetic activity of the synthesized triazinoindole bearing thiadiazole derivatives by inhibition of α-glucosidase. All synthesized analogues showed outstanding inhibition of α-glucosidase enzyme with IC50 values ranging from 2.5 ± 0.10 to 38.10 ± 0.10 µM as compared to the standard drug acarbose (IC50 = 38.45 ± 0.80 µM). Analogue 4 (IC50 = 2.5 ± 0.10 µM) was identifies as the most potent analogue in the series with fifteen folds more active than standard acarbose. Structure activity relationship (SAR) studies suggested that α-glucosidase activities of triazinoindole bearing thiadiazole are primarily dependent upon on number and position of different substitutions present on phenyl parts. Molecular docking study were conducted of the optimized compounds (i.e., compound 4, 6, and 3 etc. using MOE default parameters), the results revealed that compound 4, 6, and 3 showed numerous key interactions with the target protein, which indicate the high potential of these compounds against the target compound. All these compounds were screened for cytotoxic activity against normal normal Vero cell line and found non-toxic.

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