Synthesis, biological activity and molecular docking of new tricyclic series as α-glucosidase inhibitors

• Published in: BMC Chemistry
• Main Author: Abuelizz H.A.; Iwana N.A.N.I.; Ahmad R.; Anouar E.-H.; Marzouk M.; Al-Salahi R.
• Format: Article
• Language: English
• Published: BioMed Central Ltd 2019
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85070683368&doi=10.1186%2fs13065-019-0560-4&partnerID=40&md5=187e614587e1c2828d7c8b4148f0451a

Diabetes is an emerging metabolic disorder. α-Glucosidase inhibitors, such as acarbose, delay the hydrolysis of carbohydrates by interfering with the digestive enzymes. This action decreases the glucose absorption and the postprandial glucose level. We have synthesized 25 tricyclic 2-phenoxypyrido[3,2-e][1,2,4]triazolo[1,5-A]pyrimidin-5(4H)-ones hybrids and evaluated their α-glucosidase inhibitory activity. Compounds 6h and 6d have shown stronger activity than that of acarbose. Compound 6h exhibited the highest inhibition with an IC50 of 104.07 uM. Molecular modelling studies revealed that compound 6h inhibits α-glucosidase due to the formation of a stable ligand-α-glucosidase complex and extra hydrogen bond interactions, and directed in the binding site by Trp329.25 tricyclic 2-phenoxypyrido[3,2-e][1,2,4]triazolo[1,5-A]pyrimidin-5(4H)-ones hybrids have been synthesized and evaluated their α-glucosidase inhibitory activity. Compounds 6h have shown stronger activity than that of acarbose. © 2019 BioMed Central Ltd.. All rights reserved.