苗药喔嘎良抗真菌物质基础及其机制研究

Miao traditional medicine - Oh Ga Liang is an empirical formula which has been used for athlete’s foot. This medicine is effective and the treatment is simple and efficient, it has been used for hundreds of years. . Our early research shows: Oh Ga Liang belongs to Labiatae family and Isodon genus, it was identified as Isodon flavida (Hand.-Mazz.)Hara; The MeOH extract from this plant has a great antimicrobial activity; under active experiment, we tracked a novel compound (Fladin A) which has a peculiar structure and preferential antifungal activity. The MIC of Fladin A to Candida albicans is 36.6µg/ml, and Trichophyton rubrum is 22.5µg/ml (the MIC of clotrimazole is 0.25µg/ml). It shows great activity. Flain A is a diterpenoid which has a totally different structure with clotrimazole and ketoconazole. This indicates that Fladin A may have a new target and mechanism. HPLC analysis indicated that the MeOH extract has a large number of this kind of compounds and has a great research value and significance. This project is on the basis of previous work, through active tracking and chemical oriented combination. Our aim is to find out better antifungal active components, and discuss the structure-activity relationship, the targets and mechanisms, to research and develop a completely different structure with the medicine in market like ketoconazole and listed new antifungal drugs and lay the foundation for these new antifungal drugs.

苗药喔嘎良是贵州苗族地区用于治疗脚气病的单方药材，治疗简单、疗效突出，已有上百年的药用历史。. 课题组前期研究发现：喔嘎良为唇形科香茶菜属植物淡黄香茶菜Isodon flavida ；其醇提物显示了抗真菌活性；在活性追踪下从中分离到一个结构奇特的新化合物Fladin A，对白色念珠菌和红色毛癣菌MIC分别为36.6、22.5µg/ml（阳性药物克霉唑MIC为0.25µg/ml），表现出较好的活性。Fladin A是二萜类化合物，与克霉唑、酮康唑等上市药品的分子结构完全不同，极可能有全新的作用靶点和机制。初步的HPLC分析表明，醇提物中尚存在大量该类化合物，有深入研究的价值和意义。本课题拟在前期工作基础上，通过活性追踪和化学导向结合，期望获得抗真菌作用更强的活性物质，并探讨其构效关系、作用靶点和机制，为研发结构类型完全不同于酮康唑等上市药品的新型抗真菌药物奠定基础。

本项目以贵州苗族地区用于治疗脚气病的单方药材——淡黄香茶菜Isodon flavida (Hand.- Mazz.) Hara为研究对象，对其枝叶的化学成分和分离到的新化合物的活性进行系统深入的研究。课题在实施过程中，严格按照国家基金委对项目的管理办法，严格按照课题合同任务书的研究内容、研究目标、经费预算和考核指标执行。 .本项目较好地完成了两个不同地区产淡黄香茶菜化学成分的研究工作，从其枝叶中共分离到40个化合物，其中新化合物8个；发表研究论文6篇，其中SCI论文2篇，核心期刊论文1篇；培养硕士研究生3名；发现3个具有潜在抗菌活性的单体化合物。项目的新发现对寻找和研发具有自主知识产权的创新药物，提供了新的理念和先导化合物。.本项目的实施完成对淡黄香茶菜资源的利用开发提供了科学依据，为开发新型的抗真菌药物奠定科学基础。.综上所述，项目基本完成了合同规定的考核指标。