Structural correlation and computational quantum chemical optimization of two 1,2,3-triazolyl-methoxypyridine derivatives fused with a five-membered heterocyclic moiety, furan (I) or thiophene (II), were performed. Compounds I and II belong to the triclinic crystal classification with P-1 space group. The bond lengths and angles of the optimized crystal structures are in good agreement with the XRD experimental data. We confirmed the hydrogen bonding interactions that observed in crystal packing of compounds I and II using Hirshfeld surface and energy framework analysis. The DFT functional non-linear optical and thermochemistry parameters of the title compounds were calculated. The local reactivity domains of compounds I and II were recognized by the Fukui function parameter analysis. In silico molecular docking simulations were carried out to discover the lanosterol 14 α-demethylase (CYP51) enzyme inhibition against target protein (PDB ID: 1EA1). Antifungal activity of the title molecules was predicted by in vitro antifungal studies against three fungal strains using fungal drug fluconazole as a positive control. Compound I exhibited enhanced affinity with receptor 1EA1 and higher inhibition activity with fungal strains compared to compound II.

中文翻译：

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两种 1,2,3-三唑基-甲氧基吡啶衍生物作为 CYP51 抗真菌抑制剂的结构相关性和计算量子化学探索

进行了与五元杂环部分、呋喃 (I) 或噻吩 (II) 融合的两种 1,2,3-三唑基-甲氧基吡啶衍生物的结构关联和计算量子化学优化。化合物I和II属于具有P-1空间群的三斜晶体分类。优化后的晶体结构的键长和角度与XRD实验数据非常吻合。我们使用 Hirshfeld 表面和能量框架分析证实了在化合物 I 和 II 的晶体堆积中观察到的氢键相互作用。计算了标题化合物的 DFT 功能非线性光学和热化学参数。Fukui 函数参数分析识别了化合物 I 和 II 的局部反应域。进行了计算机分子对接模拟以发现羊毛甾醇 14 α-脱甲基酶 (CYP51) 酶对靶蛋白 (PDB ID: 1EA1) 的抑制作用。使用真菌药物氟康唑作为阳性对照，通过针对三种真菌菌株的体外抗真菌研究来预测标题分子的抗真菌活性。与化合物 II 相比，化合物 I 与受体 1EA1 的亲和力增强，对真菌菌株的抑制活性更高。