新型诺卜醇衍生 1,3,4-噻二唑-硫脲化合物的合成、抗真菌活性及 3D-QSAR 研究。
Synthesis, Antifungal Activity, and 3D-QSAR Study of Novel Nopol-Derived 1,3,4-Thiadiazole-Thiourea Compounds.
机构信息
School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China.
出版信息
Molecules. 2021 Mar 18;26(6):1708. doi: 10.3390/molecules26061708.
A series of novel nopol derivatives bearing the 1,3,4-thiadiazole-thiourea moiety were designed and synthesized by multi-step reactions in search of potent natural product-based antifungal agents. Their structures were confirmed by FT-IR, NMR, ESI-MS, and elemental analysis. Antifungal activity of the target compounds was preliminarily evaluated by in vitro methods against f. sp. , , , , , , , and at 50 µg/mL. All the target compounds exhibited better antifungal activity against , , and . Compound (R = , -Cl Ph) showed the best broad-spectrum antifungal activity against all the tested fungi. Compounds (R = -Me Ph), (R = -Pr), and (R = -Cl Ph) had inhibition rates of 86.1%, 86.1%, and 80.2%, respectively, against , much better than that of the positive control chlorothalonil. Moreover, compounds (R = -Cl Ph) and (R = -CF Ph) held inhibition rates of 80.6% and 79.0% against and , respectively, much better than that of the commercial fungicide chlorothalonil. In order to design more effective antifungal compounds against , analysis of the three-dimensional quantitative structure-activity relationship (3D-QSAR) was carried out using the CoMFA method, and a reasonable and effective 3D-QSAR model ( = 0.992, = 0.753) has been established. Furthermore, some intriguing structure-activity relationships were found and are discussed by theoretical calculation.
为了寻找有效的天然产物来源的抗真菌剂，我们设计并通过多步反应合成了一系列含有 1,3,4-噻二唑-硫脲部分的新型 nopol 衍生物。通过傅里叶变换红外光谱（FT-IR）、核磁共振（NMR）、电喷雾质谱（ESI-MS）和元素分析等方法对目标化合物的结构进行了确认。采用体外方法初步评价了目标化合物对 f. sp. 、 、 、 、 、 和 等 10 种植物病原真菌的抑制活性，其浓度为 50 µg/mL。所有目标化合物对 、 和 显示出较好的抗真菌活性。化合物 （R =, -Cl Ph）对所有测试真菌显示出最好的广谱抗真菌活性。化合物 （R = -Me Ph）、 （R = -Pr）和 （R = -Cl Ph）对 的抑制率分别为 86.1%、86.1%和 80.2%，优于阳性对照药剂百菌清。此外，化合物 （R = -Cl Ph）和 （R = -CF Ph）对 和 的抑制率分别为 80.6%和 79.0%，优于商品化杀菌剂百菌清。为了设计更有效的抗真菌化合物来防治 ，我们采用 CoMFA 方法进行了三维定量构效关系（3D-QSAR）分析，并建立了一个合理有效的 3D-QSAR 模型（ = 0.992， = 0.753）。此外，通过理论计算还发现了一些有趣的构效关系，并进行了讨论。
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