药学学报, 2018, 53(9): 1518-1525
引用本文:
李生彬, 齐慧, 张超超, 刘振明, 宋亚丽, 乔晓强. (E)-3-{[(1,3,4-噻二唑-2-基)氨基]亚甲基}-硫色满-4-酮类化合物的合成、抗真菌活性测定及分子对接研究[J]. 药学学报, 2018, 53(9): 1518-1525.
LI Sheng-bin, QI Hui, ZHANG Chao-chao, LIU Zhen-ming, SONG Ya-li, QIAO Xiao-qiang. Synthesis, antifungal activity and molecular docking of (E)-3-(((1,3,4-thiadiazol-2-yl)amino)methylene)-thiochroman-4-ones[J]. Acta Pharmaceutica Sinica, 2018, 53(9): 1518-1525.

(E)-3-{[(1,3,4-噻二唑-2-基)氨基]亚甲基}-硫色满-4-酮类化合物的合成、抗真菌活性测定及分子对接研究
李生彬1, 齐慧1, 张超超1, 刘振明3, 宋亚丽1, 乔晓强1,2
1. 河北大学 药学院, 河北省药物质量分析控制重点实验室, 河北 保定 071002;
2. 河北大学 药物化学与分子诊断教育部重点实验室, 河北 保定 071002;
3. 北京大学药学院天然药物及仿生药物国家重点实验室药物设计中心, 北京 100191
摘要:
1,3,4-噻二唑和硫色满酮是具有广泛生物活性的杂环,为寻找具有抗真菌生物活性的新颖化合物,本文合成了21个含有1,3,4-噻二唑片段的硫色满酮类衍生物。所合成的化合物经HR-MS、1H NMR、13C NMR和1D-noesy等方法进行了结构表征。采用微量稀释法对所合成的化合物进行抗真菌活性的测定,测试结果表明,化合物5j对辣椒炭疽病菌、小麦纹枯病菌、花生冠腐病菌的抑制活性均优于阳性对照药物多菌灵。化合物5h对白色念珠菌和烟曲霉的最小抑菌浓度分别为8 μg·mL-1和16 μg·mL-1,优于阳性对照药物氟康唑。利用分子对接方法研究了含1,3,4-噻二唑片段的硫色满酮类化合物与白色念珠菌的甾醇14α-去甲基化酶(sterol 14α-demethylase,CYP51)作用模式,为进一步的结构改造提供了依据。
关键词:    抗菌活性      硫色满酮      噻二唑     
Synthesis, antifungal activity and molecular docking of (E)-3-(((1,3,4-thiadiazol-2-yl)amino)methylene)-thiochroman-4-ones
LI Sheng-bin1, QI Hui1, ZHANG Chao-chao1, LIU Zhen-ming3, SONG Ya-li1, QIAO Xiao-qiang1,2
1. Key Laboratory of Pharmaceutical Quality Control of Hebei Province, College of Pharmaceutical Sciences, Hebei University, Baoding 071002, China;
2. Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding 071002, China;
3. Drug Design Center, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
Abstract:
Thiochromanones and 1,3,4-thiadazoles as heterocyclic compounds have broad biological activities. In order to find novel compounds with antifungal activity, we synthesized a novel series of (E)-3-(((1,3,4-thiadiazol-2-yl) amino)methylene)-thiochroman-4-ones. Structures of these compounds were established by HR-MS, 1H NMR, 13C NMR and 1D-noesy. All of the synthesized compounds were screened for antifungal activity by using an established agar double dilution method (plate method) against ten fungi species in vitro. Compound 5j showed significant inhibitory activity to Colletotrichum capsici, Rhizoctonia cerealis and Aspergillus niger compared with that of the positive control carbendazim. Compounds 5h exhibited better antifungal activity to Canidia albicans and Aspergillus funigatus than the positive control fluconazole, in which the minimum inhibition concentration can reach 8 μg·mL-1 and 16 μg·mL-1. Moreover, the molecular docking method was used to study the interaction mode of compound 5h and CYP51, and the results will be helpful for designing of CYP51 inhibitors in the future.
Key words:    antifungal activity    thiochromanone    1,3,4-thiadiazol   
收稿日期: 2018-04-09
DOI: 10.16438/j.0513-4870.2018-0310
基金项目: 国家自然科学基金资助项目(21675039);中国博士后科学基金资助项目(2016M591401);河北省青年拔尖人才项目;河北省自然科学基金资助项目(B2018201269);河北大学杰出青年科学基金资助项目(2015JQ06).
通讯作者: 宋亚丽,Tel/Fax:13483283338,E-mail:yalisong@hbu.edu.cn;乔晓强,Tel/Fax:15903120430,E-mail:xiaoqiao@hbu.edu.cn
Email: yalisong@hbu.edu.cn;xiaoqiao@hbu.edu.cn
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