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

A novel series of benzopyran derivatives 4 , 5 , and 6a-i was synthesized via cyclocondensation reac-tion 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 ( 1 H NMR, 13 C NMR, and HRMS) and were assessed for their inhibitory potential on the alpha-amylase enzyme. Re-sults showed that all the synthesized derivatives displayed potent alpha-amylase inhibitory activity. Com-pound 6c (IC50 = 20.38 +/- 0.79 mu M) with a pyrrolidinedione moiety bearing a phenyl ring exhibited the highest activity compared to standard acarbose (IC50 = 21.84 +/- 1.06 mu M). The mode of inhibition of alpha-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. (c) 2022 Published by Elsevier B.V.

Automated summary

A series of benzopyran derivatives 4, 5, and 6a-i were synthesized through a cyclocondensation reaction. The synthesized compounds were characterized and evaluated for their inhibitory potential on the alpha-amylase enzyme. The results showed potent alpha-amylase inhibitory activity, with compound 6c exhibiting the highest activity compared to the standard acarbose.