Huang Mei, Duan Wen-Gui, Lin Gui-Shan, Li Bao-Yu
School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China.
Guangxi Research Institute of Chemical Industry Co., Ltd., Nanning 530001, China.
Molecules. 2021 Nov 17;26(22):6948. doi: 10.3390/molecules26226948.
A series of novel menthol derivatives containing 1,2,4-triazole-thioether moiety were designed, synthesized, characterized structurally, and evaluated biologically to explore more potent natural product-based antifungal agents. The bioassay results revealed that at 50 μg/mL, some of the target compounds exhibited good inhibitory activity against the tested fungi, especially against . Compounds (R = -CH Ph), (R = -Cl Ph), (R = ,-OCH Ph) and (R = -furyl) had inhibition rates of 93.3%, 79.4%, and 79.4%, respectively, against , much better than that of the positive control chlorothalonil. Compounds (R = ,-OCH Ph) and (R = -Cl Ph) held inhibition rates of 82.4% and 86.5% against and , respectively, much better than that of the commercial fungicide chlorothalonil. Compound (R = -CH Ph) displayed antifungal activity of 90.5% and 83.8%, respectively, against and f. sp. . Compounds (R = -I Ph) had inhibition rates of 88.6%, 80.0%, and 88.0%, respectively, against f. sp. , and . Furthermore, compound (R = -CH Ph) showed the best and broad-spectrum antifungal activity against all the tested fungi. To design more effective antifungal compounds against , 3D-QSAR analysis was performed using the CoMFA method, and a reasonable 3D-QSAR model ( = 0.991, = 0.514) was established. The simulative binding pattern of the target compounds with cytochrome P450 14α-sterol demethylase (CYP51) was investigated by molecular docking.
设计、合成了一系列含有1,2,4-三唑-硫醚部分的新型薄荷醇衍生物，对其进行了结构表征和生物学评价，以探索更有效的基于天然产物的抗真菌剂。生物测定结果表明，在50μg/mL时，一些目标化合物对测试真菌表现出良好的抑制活性，尤其是对……化合物（R = -CH₂Ph）、（R = -Cl₂Ph）、（R = -OCH₃Ph）和（R = -呋喃基）对……的抑制率分别为93.3%、79.4%和79.4%，远优于阳性对照百菌清。化合物（R = -OCH₃Ph）和（R = -Cl₂Ph）对……和……的抑制率分别为82.4%和86.5%，远优于市售杀菌剂百菌清。化合物（R = -CH₂Ph）对……和……f. sp.……的抗真菌活性分别为90.5%和83.8%。化合物（R = -I₂Ph）对……f. sp.……、……和……的抑制率分别为88.6%、80.0%和88.0%。此外，化合物（R = -CH₂Ph）对所有测试真菌表现出最佳的广谱抗真菌活性。为了设计针对……的更有效的抗真菌化合物，使用CoMFA方法进行了3D-QSAR分析，并建立了合理的3D-QSAR模型（R² = 0.991，q² = 0.514）。通过分子对接研究了目标化合物与细胞色素P450 14α-甾醇脱甲基酶（CYP51）的模拟结合模式。
