Synthesis, in vitro α-glucosidase inhibitory potential and molecular docking study of thiadiazole analogs

• Published in: Bioorganic Chemistry
• Main Author: Javid M.T.; Rahim F.; Taha M.; Rehman H.U.; Nawaz M.; wadood A.; Imran S.; Uddin I.; Mosaddik A.; Khan K.M.
• Format: Article
• Language: English
• Published: Academic Press Inc. 2018
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85044438335&doi=10.1016%2fj.bioorg.2018.03.022&partnerID=40&md5=a6ede95c89d954b150d814bae0bde0db

α-Glucosidase is a catabolic enzyme that regulates the body's plasma glucose levels by providing energy sources to maintain healthy functioning. 2-Amino-thiadiazole (1–13) and 2-amino-thiadiazole based Schiff bases (14–22) were synthesized, characterized by 1H NMR and HREI-MS and screened for α-glucosidase inhibitory activity. All twenty-two (22) analogs exhibit varied degree of α-glucosidase inhibitory potential with IC50 values ranging between 2.30 ± 0.1 to 38.30 ± 0.7 μM, when compare with standard drug acarbose having IC50 value of 39.60 ± 0.70 μM. Among the series eight derivatives 1, 2, 6, 7, 14, 17, 19 and 20 showed outstanding α-glucosidase inhibitory potential with IC50 values of 3.30 ± 0.1, 5.80 ± 0.2, 2.30 ± 0.1, 2.70 ± 0.1, 2.30 ± 0.1, 5.50 ± 0.1, 4.70 ± 0.2, and 5.50 ± 0.2 μM respectively, which is many fold better than the standard drug acarbose. The remaining analogs showed good to excellent α-glucosidase inhibition. Structure activity relationship has been established for all compounds. The binding interactions of these compounds were confirmed through molecular docking. © 2018 Elsevier Inc.