Abstract

ANTIBACTERIAL ACTIVITY, MOLECULAR DOCKING, IN-SILICO ADME, AND TOXICITY STUDIES: SYNTHESIS OF N-(4- NITROBENZYL) ANILINE AND N-(4-NITROBENZYLIDENE) ANILINE

Shailesh S. Gurav*, Seema R. Jadhav, Pranaya P. Iswalkar

Abstract

In the present investigation, two compounds, 4-methyl-N-(4- nitrobenzylidene) aniline (3) and 4-methyl-N-(4- nitrobenzyl)aniline (4), were successfully synthesized through an efficient synthetic method and obtained in good yields. Synthesized Schiff base was further reduced via NaBH4, and their structures were confirmed by[1] H NMR spectra. Synthesized compounds displayed broad-spectrum antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Klebsiella pneumoniae with moderate to good inhibitory effects. Compound 3 showed good antibacterial potency against S. aureus (24 mm) and K. pneumoniae (20 mm). Further, molecular docking studies against the target protein (PDB ID: 1KZN, E. coli) exhibited good binding affinity (docking scores of -7.7 and -7.4 kcal/mol) with diverse binding interactions with active-site residues. ADME prediction revealed satisfactory pharmacokinetic rofiles for both compounds, including high gastrointestinal absorption, BBB permeability, and nonsubstrate behavior toward P-glycoprotein. Further, zero Lipinski rule violations and a bioavailability score of 0.55, suggesting good oral drug-likeness. Overall, both compounds exhibited promising antibacterial activity, favorable binding interactions, pharmacokinetic and toxicity properties, thus representing promising scaffolds for further study and biological evaluation.

Keywords: 4-methyl-N-(4-nitrobenzyl)aniline, toxicity, antibacterial activity, molecular docking, in-silico ADME.