Synthesis, Antifungal Activity, and Molecular Docking Study of Novel 3-Carene-Derived 4-Substituted Phenyl-1,2,4-Triazolinthiones Bearing gem-Dimethylcyclopropane Moiety
Synthesis, Antifungal Activity, and Molecular Docking Study of Novel 3-Carene-Derived 4-Substituted Phenyl-1,2,4-Triazolinthiones Bearing gem-Dimethylcyclopropane Moiety
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新型3-蒈烯衍生的带有宝石-二甲基环丙烷部分的4-取代苯基-1,2,4-三唑啉硫酮的合成、抗真菌活性和分子对接研究
DOI：
10.1002/cbdv.202200726
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发表时间：
2022
影响因子：
2.9
通讯作者：
Zhaolei Zhang
中科院分区：
文献类型：
--
作者：
Baoyu Li;Youpei Yu;Wengui Duan;Guishan Lin;Rongzhu Wen;Zhaolei Zhang
为探索具有抗真菌活性的新型天然先导化合物，合成了15个3-取代苯基-1，2，4-三唑啉硫酮7a，7 b，7 c，并通过UV/维斯，FT-IR，1H-NMR，13 C-NMR，ESI-MS和元素分析进行了结构表征.在50 μg/mL浓度下，对8种供试真菌进行了初步的体外抑菌活性测定，结果表明，所有目标化合物对8种供试真菌均表现出一定的体外抑菌活性，其中化合物7 g（R=m，p-Cl）对P的抑制活性最高，达85.0%。 piricolathan阳性对照百菌清。通过同源模建，构建了合理有效的植物真菌CYP 51的三维结构。分子对接结果显示，所有目标化合物的总得分均高于丙硫菌唑。此外，发现化合物7 g可以容易地嵌入结合位点，并且其中具有与丙硫菌唑类似的相互作用。因此，化合物7作为抗真菌先导化合物值得进一步研究。
For exploring new natural product‐based leading compounds with antifungal activity, 15 novel 3‐carene‐derived 4‐substituted phenyl‐1,2,4‐triazolinthiones7a∼7obearinggem‐dimethylcyclopropane moiety were synthesized and structurally characterized by UV/VIS, FT‐IR,1H‐NMR,13C‐NMR, ESI‐MS and elemental analysis. The preliminary bioassay at 50 μg/mL showed that all of the target compounds exhibited certainin vitroinhibitory activities against the eight tested fungi, in which compound7g(R=m,p‐Cl) displayed better inhibition activity (85.0 %) againstP. piricolathan that of the positive control Chlorothalonil. Furthermore, a reasonable and effective 3D structure of phytofungal CYP51 was constructed by homology modeling. Molecular docking study revealed that the total scores of all the target compounds were higher than that of Prothioconazole. In addition, it was found that compound7gcould readily embed into the binding site, and therein shared similar interactions with the case of Prothioconazole. Thus, compound7gdeserved further study as an antifungal leading compound.