Synthesis, characterization, and in vitro and in silico α-glucosidase inhibitory evolution of novel N′-(2-cyclopentyl-2-phenylacetyl)cinnamohydrazide derivatives

Abstract

To discover potential α-glucosidase inhibitory agents, a new series of N′-(2-cyclopentyl-2-phenylacetyl)cinnamohydrazide derivatives were designed and synthesized as α-glucosidase inhibitors. The newly synthesized compounds were characterized using ¹H, ¹³C NMR, and mass spectroscopy analysis and evaluated for their in vitro α-glucosidase inhibitory effects. All the tested compounds displayed significant α-glucosidase inhibitory activity compared to the standard drug acarbose. Among all, compounds 7b, 7d and 6g exhibited the strongest inhibition with IC₅₀ values of 14.48 nmol, 18.88 nmol and 28.51 nmol, respectively. Molecular docking analysis was conducted to identify the important binding interactions responsible for inhibition activity of a-glucosidase. The compounds 7b and 7d exhibit the highest docking energies, with same value of −10.1 kcal mol⁻¹ with crucial hydrogen bonding interactions with HIS:280 and ASN:415, respectively. Furthermore, computational drug likeness/ADME/toxicity analysis was conducted on the compounds, which indicated that these compounds exhibit drug-like properties and possess favourable ADME and toxicity profiles.