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8μg·m L^(-1)和16μg·m L^(-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。
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, 1 H NMR, 13 C NMR and 1 D-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 5 j showed significant inhibitory activity to Colletotrichum capsici, Rhizoctonia cerealis and Aspergillus niger compared with that of the positive control carbendazim. Compounds 5 h 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·m L^（-1） and 16 μg·m L^（-1）. Moreover, the molecular docking method was used to study the interaction mode of compound 5 h and CYP51, and the results will be helpful for designing of CYP51 inhibitors in the future.
作者
李生彬
齐慧
张超超
刘振明
宋亚丽
乔晓强
LI Sheng-bin;QI Hui;ZHANG Chao-chao;LIU Zhen-ming;SONG Ya-li;QIAO Xiao-qiang(Key Laboratory of Pharmaceutical Quality Control of Hebei Province,College of Pharmaceutical Sciences;Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education,Hebei University,Baoding 071002,China;Drug Design Center,State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University,Beijing 100191,China)
出处
《药学学报》
CAS
CSCD
北大核心
2018年第9期1518-1525,共8页
Acta Pharmaceutica Sinica
基金
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)
关键词
抗菌活性
硫色满酮
噻二唑
antifungal activity
thiochromanone
1,3,4-thiadiazol
