New Antimalarials from Plant-Pathogenic Fungi

来自植物病原真菌的新型抗疟药

• 批准号: 6899703
• 负责人: NP D NANAYAKKARA
• 金额: $ 17.94万
• 依托单位: UNIVERSITY OF MISSISSIPPI
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6899703
• 关键词: Plasmodium falciparum; antimalarial agents; bioassay; biological products; drug discovery /isolation; drug resistance; drug screening /evaluation; herbicides; laboratory mouse; malaria; microorganism metabolism; mycotoxins; pharmacokinetics; tissue /cell culture

DESCRIPTION (provided by the applicant): Plasmodium falciparum, which often causes fatal cerebral malaria, especially among children, has developed resistance to the one very effective antimalarial drug chloroquine and is developing resistance to other antimalarial drugs introduced more recently such as mefloquine and halofantrin. Therefore, there is an urgent need to develop alternative drugs to counter this trend. Natural products isolated from higher plants, such as quinine and artemisinin, have provided effective drugs against malaria. In the last few decades a large number of plants, including those traditionally used, have been evaluated for their antimalarial activity. However, no new drug candidates and very few lead compounds have emerged from these efforts. Because of the ease of rapid mass production and good chemical diversity, fungi remain a good and attractive natural source for biologically active compounds. Fungi have provided the majority of agents and lead compounds currently used against bacterial infections. A few of these antibiotics are effective in combination with conventional antimalarial drugs against drug-resistant falciparum malaria. However, only very few extracts or secondary metabolites of fungi have been systematically evaluated for their antimalarial activity. Plant pathogenic fungi are known to release phytotoxic secondary metabolites, which disrupt biochemical processes in plant cells. Genomic and recent biochemical studies have shown that there are a number of plant-like metabolic pathways in the malaria parasite. Our preliminary results indicate that plant pathogenic fungi can be a good source of antimalarial compounds. The purpose of this proposal is to expand on these results and to identify antimalarial compounds from plant pathogenic fungi and their preliminary evaluation as new clinically useful antimalarial agents.

描述（由申请人提供）：恶性疟原虫经常导致致命的脑疟疾，特别是在儿童中，已对一种非常有效的抗疟药物氯喹产生耐药性，并正在对最近引入的其他抗疟药物（如甲氟喹和氟苯醚）产生耐药性。因此，迫切需要开发替代药物来应对这一趋势。

项目成果

Biologically active tetranorditerpenoids from the fungus Sclerotinia homoeocarpa causal agent of dollar spot in turfgrass.

• DOI: 10.1021/np900334k
• 发表时间: 2009-12
• 期刊: JOURNAL OF NATURAL PRODUCTS
• 影响因子: 5.1
• 作者: Herath, H. M. T. Bandara;Herath, Wimal H. M. W.;Carvalho, Paulo;Khan, Shabana I.;Tekwani, Babu L.;Duke, Stephen O.;Tomaso-Peterson, Maria;Nanayakkara, N. P. Dhammika
• 通讯作者: Nanayakkara, N. P. Dhammika