Synthesis of Bis-indolylmethane sulfonohydrazides derivatives as potent α-Glucosidase inhibitors

• Published in: Bioorganic Chemistry
• Main Author: Gollapalli M.; Taha M.; Ullah H.; Nawaz M.; AlMuqarrabun L.M.R.; Rahim F.; Qureshi F.; Mosaddik A.; Ahmat N.; Khan K.M.
• Format: Article
• Language: English
• Published: Academic Press Inc. 2018
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85048198591&doi=10.1016%2fj.bioorg.2018.06.001&partnerID=40&md5=c8d5a64c98a4ca54fd171e31db6fbd90

In search of better α-glucosidase inhibitors, a series of bis-indolylmethane sulfonohydrazides derivatives (1-14) were synthesized and evaluated for their α-glucosidase inhibitory potential. All derivatives exhibited outstanding α-glucosidase inhibition with IC 50 values ranging between 0.10 ± 0.05 to 5.1 ± 0.05 μM when compared with standard drug acarbose having IC 50 value 856.28 ± 3.15 μM. Among the series, analog 7 (0.10 ± 0.05 μM) with tri-chloro substitution on phenyl ring was identified as the most potent inhibitor of α-glucosidase (∼ 8500 times). The structure activity relationship has been also established. Molecular docking studies were also performed to help understand the binding interaction of the most active analogs with receptors. From the docking studies, it was observed that all the active bis-indolylmethane sulfonohydrazides derivatives showed considerable binding interactions within the active site (acarbose inhibition site) of α-glucosidase. We also evaluated toxicity of all derivatives and found none of them are toxic. © 2018 Elsevier Inc.