Synthesis, biological evaluation and molecular docking study of novel amide-coupled naphthalene scaffolds as potent inhibitors of bacterial recombinase A

Abstract

The development of antimicrobials having a unique mode of action is essential to solve multi-drug resistance challenges. Herein, we have designed and synthesized novel amide-coupled naphthalene scaffolds (4a-l) by acid-amine coupling reaction of 2-(naphthalen-1-yloxy)acetic acid with various amines. These derivatives were evaluated for their antibacterial, antifungal and anti-malarial actions. Among all, 4g exhibited excellent antibacterial activity at minimum inhibitory concentration (MIC) values ranging between 12.5 and 100 ​μg/mL against Escherichia coli, Pseudomonas aeruginosa,Staphylococcus aureus and Streptococcus pyogenes. The antifungal assay revealed that compounds 4c, 4f and 4l were most effective (MIC - 250 ​μg/mL) against Candida albicans compared to standard drug griseofulvin. Compounds 4h and 4l manifested moderately active anti-malarial action, with mean IC50 of 0.47 and 0.48 ​μg/mL, respectively. Different naphthalene scaffolds have been known to inhibit bacterial RecA, an essential protein of DNA repair mechanism as a potential target for antibacterial drug discovery. In this context, a molecular docking study was carried out to determine the molecular binding affinity of the synthesized naphthalene scaffolds with bacterial RecA. The amino acids in the active region of bacterial RecA interacted effectively with the synthesized naphthalene scaffolds, suggesting that they could function as potent RecA inhibitors.