药学学报, 2017, 52(1): 113-119
引用本文:
韩晓燕, 李生彬, 梁国超, 周冠, 钟一凡, 齐慧, 宋亚丽, 乔晓强. N-1,3,4-噻二唑-2-基硫色满-4-酮-2-甲酰胺衍生物的合成及抗真菌活性测定[J]. 药学学报, 2017, 52(1): 113-119.
HAN Xiao-yan, LI Sheng-bin, LIANG Guo-chao, ZHOU Guan, ZHONG Yi-fan, QI Hui, SONG Ya-li, QIAO Xiao-qiang. Synthesis and antifungal activities of N-1,3,4-thiadiazol-2-yl-4-oxo-thiochroman-2-yl-formamide derivatives[J]. Acta Pharmaceutica Sinica, 2017, 52(1): 113-119.

N-1,3,4-噻二唑-2-基硫色满-4-酮-2-甲酰胺衍生物的合成及抗真菌活性测定
韩晓燕1, 李生彬1, 梁国超1, 周冠1, 钟一凡1, 齐慧1, 宋亚丽1,2, 乔晓强1,2
1. 河北大学药学院, 河北省药品质量控制重点实验室, 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
摘要:
鉴于1,3,4-噻二唑和硫色满酮类化合物均是具有广泛生物活性的杂环化合物,为寻找具有抗真菌生物活性的新颖化合物,本文以取代苯硫酚和顺丁烯二酸酐为原料,合成中间产物2-羧基-硫色满酮,再与2-氨基-1,3,4-噻二唑反应,最终合成了14个含有1,3,4-噻二唑片段的硫色满酮类衍生物。目标化合物的结构均由核磁共振氢谱(1H NMR)、核磁共振碳谱(13C NMR)和高分辨质谱(HR-MS)确证。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3a3c对絮状表皮癣菌和总状毛霉菌的最小抑菌浓度分别达到8 μg·mL-1和16 μg·mL-1,均优于阳性对照药物氟康唑。化合物3e对玉米小斑病菌、油菜菌核病菌、番茄灰霉病菌的抑制活性均优于阳性对照药物多菌灵。化合物3b对玉米小斑病菌的抑制活性优于阳性对照药物多菌灵。
关键词:    硫色满酮      1,3,4-噻二唑      微量稀释法      抗真菌活性     
Synthesis and antifungal activities of N-1,3,4-thiadiazol-2-yl-4-oxo-thiochroman-2-yl-formamide derivatives
HAN Xiao-yan1, LI Sheng-bin1, LIANG Guo-chao1, ZHOU Guan1, ZHONG Yi-fan1, QI Hui1, SONG Ya-li1,2, QIAO Xiao-qiang1,2
1. College of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding 071002, China;
2. Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding 071002, China
Abstract:
Thiochromanones and 1,3,4-thiadazoles as heterocyclic compounds have broad biological activities. In order to find novel compounds with antifungal bioactivity, substituted thiophenol and maleic anhydride were used to synthesize the intermediate 4-oxothiochromane-2-carboxylic acid. It was reacted with 2-amino-1,3,4-thiadiazol to get fourteen target compounds containing 1,3,4-thiadazole moiety. The structures of the obtained compounds were confirmed by 1H NMR, 13C NMR and HR-MS. All compounds were investigated for antifungal activity via microdilution broth method. The results showed that the target compounds 3a and 3c to Epidermophyton floccosum and Mucor racemosus exhibited better antifungal activity than the positive control fluconazole, in which the minimum inhibition concentration can reach 8 μg·mL-1 and 16 μg·mL-1. Compound 3e showed significant inhibitory activity to Helminthosporium maydis, Sclerotinia sclerotiorum and Botrytis cinerea compared with that of the positive control carbendazim. Compound 3b exhibited inhibitory activity to Helminthosporium maydis better than the positive control carbendazim.
Key words:    thiochromanone    1,3,4-thiadazole    microdilution broth method    antifungal activity   
收稿日期: 2016-10-20
DOI: 10.16438/j.0513-4870.2016-1023
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(B2015201016);河北大学杰出青年科学基金资助项目(2015JQ06);河北大学实验室开放项目(sy201617).
通讯作者: 宋亚丽,Tel:13483283338,E-mail:yalisong@hbu.edu.cn;乔晓强,Tel:15903120430,E-mail:xiaoqiao@hbu.edu.cn
Email: yalisong@hbu.edu.cn;xiaoqiao@hbu.edu.cn
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