New biologically dynamic hybrid pharmacophore triazinoindole-based-thiadiazole as potent α-glucosidase inhibitors: In vitro and in silico study

• Published in: International Journal of Biological Macromolecules
• Main Author: Khan A.A.; Rahim F.; Taha M.; Rehman W.; Iqbal N.; Wadood A.; Ahmad N.; Shah S.A.A.; Ghoneim M.M.; Alshehri S.; Salahuddin M.; Khan K.M.
• Format: Article
• Language: English
• Published: Elsevier B.V. 2022
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85123935293&doi=10.1016%2fj.ijbiomac.2021.12.147&partnerID=40&md5=f9f0ebb4a27c32b7e62369ad2983c628

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. © 2021 Elsevier B.V.