Antifungal sphingolipids for AIDS-related Mycoses

抗真菌鞘脂治疗艾滋病相关真菌病

• 批准号: 6655355
• 负责人: Tadeusz F Molinski
• 金额: $ 3.8万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6655355
• 关键词: AIDS; Candida; Commonwealth of Independent States; Cryptococcus neoformans; Porifera; antifungal agents; circular dichroism; drug discovery /isolation; drug screening /evaluation; fluconazole; high performance liquid chromatography; mass spectrometry; microorganism disease chemotherapy; mycosis; nuclear magnetic resonance spectroscopy; opportunistic infections; pharmacokinetics; sphingolipids; stereochemistry; thin layer chromatography

DESCRIPTION (provided by applicant): Russia has one of the highest rates of increase in new cases of AIDS in the developed world correlated with tumultuous social and economic upheaval in the past decade. The development of novel antifungal drugs with activity against AIDS-related opportunistic fungal disease, joined with regional efforts in drug discovery, is needed. Dimeric sphingolipids, which occur in marine sponges of restricted distribution, exhibit significant synergism in antifungal assays (in vitro) and may be useful leads in development of novel antimycotics with unique or complementary modes of action to clinical drugs. This AIDS-FIRCA proposal seeks to isolate and characterize novel dimeric sphingolipids from marine sponges of the family Leucettidae. New compounds will be isolated using solvent fractionation and chromatography and characterized using a variety of spectroscopic techniques, in particular mass spectrometry nuclear magnetic resonance spectroscopy (NMR) and circular dichroism (CD). Biological activity of pure antifungal compounds will be characterized using in vitro antifungal susceptibility testing in panel of fluconazole-resistant fungi. Lead compounds will be selected for advanced in vivo evaluation in murine models of fungemia.

描述（由申请人提供）： 在过去十年中，俄罗斯在发达国家的新艾滋病案例中的增长率之一与动荡的社会和经济动荡相关。需要与艾滋病相关的机会真菌疾病进行活性的新型抗真菌药物的发展，并与药物发现的区域努力一起发展。二聚体鞘脂发生在限制分布的海洋海绵中，在抗真菌测定中表现出显着的协同作用（体外），并且在开发具有独特或互补作用方式的新型抗虫子方面可能是有用的铅。该AIDS-FIRCA提案试图将新型二聚体鞘脂与Leucettidae家族的海洋海绵分离出来。新化合物将使用溶剂分馏和色谱分离，并使用各种光谱技术，特别是质谱法核磁共振光谱（NMR）和圆形二科主义（CD）来表征。纯抗真菌化合物的生物学活性将使用体外抗真菌敏感性测试在抗氟康唑耐药的真菌中进行表征。将在真菌鼠模型中选择铅化合物进行晚期体内评估。