Green One-Pot Synthesis, Docking, ADMET and Antibacterial Evaluation of 1,4-Dihydropyrano[2,3-c]pyrazole Derivatives

Abstract

Environmentally benign, time-efficient and straightforward methodologies have been developed for the synthesis of fused pyranopyrazole derivatives via a one-pot four-multicomponent reaction (MCR). Two synthetic approaches were employed using aromatic aldehydes, ethyl acetoacetate, malononitrile and hydrazine hydrate with L-histidine serving as an effective organocatalyst. In method I, the reaction was carried out in aqueous medium at 85 ºC, affording the desired product with a yield of 93%. In method II, a solvent-free approach utilizing different mole ratio of the same catalyst achieved a comparable yield of 92% within 5 min, demonstrating the efficiency of the protocol. The structures of the synthesized pyranopyrazole derivatives were confirmed using spectroscopic techniques including UV, FT-IR, ¹H NMR and ¹³C NMR. The physico-chemical and pharmacokinetic properties were evaluated using the freely accessible SwissADME web server. Furthermore, molecular docking studies were performed using AutoDock and Molegro Molecular Viewer to assess the binding interactions of the synthesized compounds with glucosamine-6-phosphate synthase (GlmS), a validated antibacterial target. The docking results suggest the potential inhibitory activity against several tested bacterial strains.