A series of triazoles as miconazole analogues was designed, synthesized and characterized by IR, NMR, MS and HRMS. All the newly prepared compounds were screened for their antifungal activities against five kinds of fungi. The bioactive assay showed that most of the synthesized compounds exhibited good or even stronger antifungal activities in comparison with the reference drugs miconazole and fluconazole. In particular, the 3,4-dichlorobenzyl derivative 5b showed a comparable or superior activity against all the tested fungal strains to standard drugs, and formed a supramolecular complex with CYP51 via the hydrogen bond between the 4-nitrogen of the triazole nucleus and the histidine residue. Preliminary experiments revealed that both of the active molecules 5b and 9c could intercalate into calf thymus DNAs, which might block DNA replication to exhibit their powerful antifungal abilities. Further studies indicated that compound 5b might be stored and transported by human serum albumin through hydrophobic interactions, specific electrostatic interactions and hydrogen bonds. These results strongly suggested that compound 5b could serve as a promising antifungal candidate.

中文翻译：

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潜在的抗真菌三唑的发现：设计，合成，生物学评估和初步的抗真菌机理探索

设计，合成了一系列三唑类咪康唑类似物，并通过IR，NMR，MS和HRMS进行了表征。筛选所有新制备的化合物对五种真菌的抗真菌活性。生物活性测定表明，与参考药物咪康唑和氟康唑相比，大多数合成的化合物均表现出良好甚至更强的抗真菌活性。特别地，3,4-二氯苄基衍生物5b对所有测试的真菌菌株均具有与标准药物相当或更高的活性，并通过三唑核的4-氮与组氨酸之间的氢键与CYP51形成超分子复合物。残留物。初步实验表明，两种活性分子5b9c和9c可以插入小牛胸腺DNA中，这可能会阻止DNA复制以显示其强大的抗真菌能力。进一步的研究表明，化合物5b可能通过疏水相互作用，特异性静电相互作用和氢键被人血清白蛋白储存和运输。这些结果强烈暗示化合物5b可以用作有希望的抗真菌候选物。