Organocatalysed synthesis of N-(4-oxo-2-phenyl-1,2-dihydroquinazolin-3(4H)-yl)isonicotinamide: computational, electrochemical, drug-likeness and antimicrobial studies.

Abstract

We have developed novel and sustainable homogeneous catalysts employing Glutamic acid (Glu) as a biodegradable and eco-friendly organocatalyst for the synthesis of N-(4-oxo-2-phenyl-1,2-dihydroquinazolin-3(4H)-yl)isonicotinamide derivatives (5a-l) via multicomponent reactions (MCRs) of isatoic anhydride, isoniazid and heteroaromatic/aromatic aldehyde in ethanol on oil bath stirring at 60 °C. Selected final product homogeneity was examined by various spectroscopic techniques such as ¹³C-, ¹H- NMR, FT-IR and LC-MS. For the first time, herein investigated electrochemical behavior of selected derivatives (5c, 5h-l) using cyclic voltammetry method. The results of this investigation indicated compounds 5i, 5h and 5l exhibited highest levels of oxidation and reduction potential. Further, pharmacokinetic properties were assessed via SwissADME online tool, derivatives tested complied with Lipinski's rule of five for drug-likeness. Furthermore, molecular docking studies demonstrated for significant binding between the protein and ligand, and affinity values ranged from - 8.91 to - 8.45 kcal/mol, and MM/PBSA estimated high negative values suggested significant interactions between ligand and protein. Moreover, antibacterial evaluation of compounds 5i in water, and 5k in DMSO on Salmonella typhimurium showed pronounced effect with inhibition zone of 15 ± 0.6 mm and 20 ± 0.4 mm, respectively as compared to the standard tetracycline inhibition zone of 15 ± 0.5 mm.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04188-z.