Synthesis, In Vitro and In Silico Investigations of 4-(1H-Indol-3-yl)-N′-[(E/Z)-(phenyl-substituted)methylidene] as Effective Inhibitors of α-Glucosidase

Objective: The study commenced with the conversion of 4-(1H-indol-3-yl)butanoic acid (I) into ethyl 4-(1H-indol-3-yl)butanoate (II), succeeded by the synthesis of the hydrazide nucleophile, 4-(1H-indol-3-yl)butanohydrazide (III). Methods: Following this, nucleophilic addition reactions of (III) with various electrophilic aldehydes (IVa–IVg) were conducted to yield the targeted derivatives (Va–Vg/Vʹa–Vʹg). The structural elucidation of all synthesized compounds relied on IR, 1H, 13C NMR, HMBC, and CHN analysis. Results and Discussion: Evaluation of the inhibitory effects of these heterocyclic butanohydrazides (Va–Vg/Vʹa–Vʹg) against the α-glucosidase enzyme revealed significant inhibition by compounds (Vg/Vʹg) compared to the standard. Conclusions: Hemolytic analysis indicated mild cytotoxicity towards red blood cell membranes, indicating the potential of these molecules as nontoxic medicinal scaffolds for skin pigmentation and related disorders.