New Amino Acids Naphthalene Scaffolds as Potent Antimicrobial Agents: In Vitro Assay and In Silico Molecular Docking Study

Abstract

AbstractThe development of innovative antifungal medications to address the issues of indiscriminate antifungal use contributes to certain antifungal drug resistance. To tackle this issue, we have designed and synthesized novel amino acids naphthalene scaffolds (6 a–6 i) (Scheme 1) by acid amine coupling between compound 5 and various amino acids. Moreover, we evaluated the antifungal, anti‐bacterial and antimalarial activities of synthesized derivatives. Among them, compounds Met (6 a), Phe (6 c), Lys (6 d), Ser (6 f), and Tyr (6 i) expressed excellent antifungal activity at a minimum inhibitory concentration (MIC) value of 250 μg/mL against Candida albicans compared to standard drug griseofulvin (500 μg/mL). The antibacterial assay results showed that compound Met (6 a) exhibited effective antibacterial activity at MIC value at 50 and 62.5 μg/mL against Streptococcus pyogenes and Pseudomonas aeruginosa respectively, and compound Trp (6 g) showed very good antibacterial activity at MIC 62.5 μg/mL against Staphylococcus aureus. The antimalarial activity of synthesized compoundsVal (6 b) and Lys (6 d) showed moderately active with mean IC50 of 0.69 and 0.47 μg/mL, respectively compared with standard drug quinine (IC50=0.26 μg/mL). Also, a molecular docking study was performed to demonstrate the binding energy of synthesized scaffoldswith effective interaction with various proteins. The compound Met (6 a) showed that the highest binding affinity (binding energy: −7.1 kcal/mol) which interacted more effectively with VAL 120 (2.90 Å).