Design, Synthesis and biological evaluation of novel benzopyran derivatives as potential α-amylase inhibitors: An Investigation by Experimental and Computational Studies

Abstract

A novel series of benzopyran derivatives 4, 5, and 6a-i was synthesized via cyclocondensation reaction of hydrazide 3 with some electrophilic species such as 2,4-pentanedione, 2,5-hexanedione, and cyclic anhydrides. The synthesized compounds were characterized by spectroscopic means (1H NMR, 13C NMR, and HRMS) and were assessed for their inhibitory potential on the α-amylase enzyme. Results showed that all the synthesized derivatives displayed potent α-amylase inhibitory activity. Compound 6c (IC50 = 20.38 ± 0.79 µM) with a pyrrolidinedione moiety bearing a phenyl ring exhibited the highest activity compared to standard acarbose (IC50 = 21.84 ± 1.06 µM). The mode of inhibition of α-amylase by all the compounds via a kinetic study was also determined. Results indicated that they followed competitive and non-competitive modes of inhibition against the target enzyme. The molecular docking analysis reinforced the results and demonstrated that these compounds are involved in various binding interactions with the enzyme. Various physicochemical and pharmacokinetic properties of the synthesized derivatives were predicted. We noted that all the compounds are likely to be orally active as they obeyed Lipinski's rule of five, and most of the properties were found to be within the desired limits.