The 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).

中文翻译：

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新型氨基酸萘支架作为有效的抗菌剂：体外测定和计算机分子对接研究

为了解决滥用抗真菌药物问题而开发的创新抗真菌药物会导致某些抗真菌药物耐药性。为了解决这个问题，我们通过化合物5和各种氨基酸之间的酸胺偶联设计并合成了新型氨基酸萘支架(6 a–6 i)（方案1）。此外，我们评估了合成衍生物的抗真菌、抗菌和抗疟活性。其中，化合物Met（6a）、Phe（6c）、Lys（6d）、Ser（6f）和Tyr（6i）在最低抑菌浓度（MIC）值为250μg时表现出优异的抗真菌活性/mL 反对白色念珠菌与标准药物灰黄霉素 (500 μg/mL) 相比。抗菌测定结果表明，化合物Met(6a)在MIC值为50和62.5 μg/mL时表现出有效的抗菌活性。化脓性链球菌和铜绿假单胞菌分别，化合物 Trp (6 g) 在 MIC 62.5 μg/mL 下表现出非常好的抗菌活性。金黄色葡萄球菌。合成化合物 Val (6 b) 和 Lys (6 d) 的抗疟活性显示出中等活性，平均 IC 值50与标准药物奎宁相比，IC 值分别为 0.69 和 0.47 μg/mL50=0.26微克/毫升）。此外，还进行了分子对接研究，以证明合成支架的结合能与各种蛋白质的有效相互作用。化合物 Met (6 a) 显示出最高的结合亲和力（结合能：-7.1 kcal/mol），与 VAL 120 (2.90 Å) 相互作用更有效。