Synthesis, in vitro antimicrobial activity, and in silico studies of 1-aminoalkyl-2-naphthols

Abstract

The rise of multidrug-resistant (MDR) pathogens highlights the need for novel antimicrobial agents. This study reports the synthesis of two 1-aminoalkyl-2-naphthol derivatives, 1-(dimethylaminomethyl)naphthalen-2-ol (2) and 1-(piperidin-1-ylmethyl)naphthalen-2-ol (3), via the Betti base reaction using 2-naphthol, formaldehyde, and secondary amines. Structural confirmation was achieved through the 1H and 13C-NMR. Antimicrobial screening against 26 bacterial and 4 fungal strains revealed that compound 3 exhibited potent antibacterial activity against MDR strains, with a minimum inhibitory concentration (MIC) value as low as 10 µg/mL against Pseudomonas aeruginosa MDR1. Compound 3 also demonstrated superior efficacy against Staphylococcus aureus MDR strains, with an MIC of 100 µg/mL, compared to ciprofloxacin, which had an MIC of 200 µg/mL. Its lower MIC values compared to ciprofloxacin suggests that compound 3 has potential for treating infections caused by multidrug-resistant S. aureus. Compound 2 showed strong antifungal activity against Penicillium notatum and P. funiculosum, with an MIC of 400 µg/mL, outperforming griseofulvin (MIC = 500 µg/mL). Molecular docking further supported these findings, with compound 3 displaying strong binding affinities to E. coli DNA gyrase (‒6.755 kcal/mol; PDB ID: 5MMN) and Candida albicans lanosterol 14α-demethylase (‒7.813 kcal/mol; PDB ID: 5V5Z). Overall, these results underscore the potential of 1-aminoalkyl-2-naphthol derivatives as promising candidates for combating drug-resistant infections.