Candida infections pose a serious public health threat due to increasing drug resistance. Azoles are first-line antifungal drugs for fungal infections. In this study, we tested an in-house azole collection incorporating naphthalene ring to find hits against planktonic and biofilm forms of resistant Candida spp. In the collection, potent derivatives were identified against the susceptible strains of Candida with minimum inhibitory concentration (MIC) values lower than those of the reference drug, fluconazole. MIC values of 0.125 μg/ml against C. albicans, 0.0625 μg/ml against C. parapsilosis, and 2 μg/ml against C. krusei, an intrinsically azole-resistant non-albicans Candida, were obtained. Some of the derivatives were highly active against fluconazole-resistant clinical isolate of C. tropicalis. Inhibition of C. albicans biofilms was also observed at 4 μg/ml similar as amphotericin B, the reference drug known for its antibiofilm activity. Through molecular docking studies, affinities and key interactions of the compounds with fungal lanosterol 14α-demethylase (CYP51), the target enzyme of azoles, were predicted. The interactions of imidazole with heme cofactor and of the naphthalene with Tyr118 were highlighted in line with the literature data. As a result, this study proves the importance of naphthalene for the antifungal activity of azoles against Candida spp. in both planktonic and biofilm forms.

由于耐药性增加，念珠菌感染对公共健康构成严重威胁。唑类是真菌感染的一线抗真菌药物。在这项研究中，我们测试了一个包含萘环的内部唑类集合，以发现对浮游和生物膜形式的抗性念珠菌的影响。在该系列中，鉴定出针对念珠菌敏感菌株的有效衍生物，其最低抑菌浓度 (MIC) 值低于参考药物氟康唑的最低抑菌浓度 (MIC)。对白色念珠菌的MIC 值为 0.125 μg/ml ，对近平滑念珠菌的MIC 值为0.0625 μg/ml ，对克柔念珠菌（一种固有的唑类抗性非白色念珠菌）的MIC 值为2 μg/ml, 获得。一些衍生物对抗氟康唑的热带念珠菌临床分离株具有高度活性。在 4 μg/ml 浓度下也观察到了对白色念珠菌生物膜的抑制作用，类似于两性霉素 B，这是一种以其抗生物膜活性而闻名的参考药物。通过分子对接研究，预测了化合物与唑类靶酶真菌羊毛甾醇 14α-脱甲基酶 (CYP51) 的亲和力和关键相互作用。咪唑与血红素辅因子和萘与 Tyr118 的相互作用已根据文献数据得到强调。因此，这项研究证明了萘对唑类抗念珠菌的抗真菌活性的重要性。以浮游和生物膜形式存在。