耐药菌已成为全球卫生的重大威胁，而源于植物的天然产物，因其独特的结构与作用机制可望成为新型抗菌药物的重要来源。申请人前期研究发现夹竹桃科马铃果属植物民间用于治疗与感染有关等疾病，富含大量的单萜吲哚生物碱。该属植物的总生物碱具有显著的抗微生物活性，初步的植物化学研究得到3个新颖骨架和2个含量极高的单萜吲哚生物碱，部分化合物表现出显著的抗微生物活性，优于临床抗菌药物，是开发天然抗菌药物的宝贵资源。. 本项目拟对马铃果属伏康树和马铃果的果实和叶子开展深入的植物化学和抗微生物活性研究，探讨活性分子的构效关系及作用机制。采用LC-MS导向及多种柱色谱分离技术，分离鉴定不少于60个单萜吲哚生物碱活性成分；采用最低抑菌浓度评价其对产ESBLs耐药菌及普通菌株的活性；从活性分子对微生物超微结构、渗透压及生物大分子含量的影响阐明其作用机制。项目的完成将为开发植物源抗菌剂奠定实验方法及理论依据。

Resistant microbial has become a serious threat for global health, and natural compounds from plants were considered to be important resources in new generation antimicrobial drugs, owing to its distinct frameworks and action mechanisms. Previous study found that the Voacanga (Apocynaceae) were traditionally used to treat diseases associated with infection, and they are rich in monoterpene indole alkaloids (MIAs). The total alkaloids from Voacanga species showed significant antimicrobial activities, and preliminary phytochemistry investigations of which led to three novel skeletons and two very high level compounds (vobasan and vobtusine) were isolated. Biological studies showed that some compounds exhibited potent antimicrobial activity, which were superior to those of the clinical antibacterial drugs. It is a precious resource for the development of natural antibiotics.. The project will study of the fruits and leaves of two Voacanga species (V. africana and V. chalotiana), and focused on phytochemical investigations, bioactive evaluations, structure-activity relationship, and mechanisms. At least 60 MIAs with antimicrobial activities were isolated from the two plants using of LC-MS method and various kinds of chromatography columns. Adopting minimal inhibitory concentration (MIC) assay, compounds were evaluated of antimicrobial activities against the ESBLs resistant bacteria, Escherichia coli, Salmonella typhi, Bacillus subtilis, Staphyloccus aureus, Candida albicans, and Trichophyton rubrumthe strains. As mechanism research, the influences of the active compounds on the ultrastructure morphology, oncotic pressure, and macromolecular content will help us to explore the antimicrobial mechanism of MIAs. The completion of these studies will provide reliable methods and theoretical basis for development of new generation of plant-derived antimicrobial drugs.