Novel Antimalarials from Marine Microbial Natural Products

来自海洋微生物天然产物的新型抗疟药

基本信息

  • 批准号:
    8302637
  • 负责人:
  • 金额:
    $ 22.84万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-02-15 至 2014-01-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): There are over 300 million clinical episodes of malaria each year worldwide with over 1 million deaths, primarily in children under 5. Over 41% of the world's population lives in areas where malaria is transmitted. The global economic toll of malaria is staggering. In addition to contributing significantly towards overall childhood mortalit in the poorest nations, the disease is estimated to cause approximately a 1.3% reduction in economic growth in countries that bear a heavy malaria burden. Unfortunately, most of the drugs that are currently being used for malaria treatment were developed more than 30 years ago and many are derivatives of older drugs. In the absence of a large-scale effort to develop novel drugs against malaria, most antimalarials have now become ineffective due to widespread drug resistance. Investment in the discovery of new therapeutics for the treatment of malaria has been sparse and the number of new treatments introduced to the market is correspondingly low. Given the global toll of malaria and the spread of drug resistance, it is important to identif new chemical entities that can be developed into therapeutics for the treatment of drug-resistant malaria. The proposed research project seeks to discover novel chemical entities from marine microbes targeting the malaria parasite is timely and will provide entry into novel therapeutic interventions for the disease. Our approach will be to tap into the chemical and biological diversity of the Harbor Branch Oceanographic Institute Marine Microbial Culture Collection (HBMMCC) as a source of novel bioactive natural products. We will assay a novel library of marine microbe derived extracts for their ability to inhibit the growth of the malaria parasite usig the SYBR Green I Fluorescent assay. Active extracts will be dereplicated using Liquid-chromatography- mass spectroscopy (LC-MS) and NMR methodologies and those with the greatest potential for novel chemistry will be further profiled for their activity against a panel f drug resistant Plasmodium falciparum strains to define potency, and the mammalian cell lines to help assess therapeutic index. Extracts with strong potency against the malaria parasite, low toxicity to mammalian cells and novel chemistry will be taken through bioassay- guided fractionation to identify the structure of bioactive components. The proposed research is significant because at the end of this project we expect to have a portfolio of antimalarial "hits" PUBLIC HEALTH RELEVANCE: Malaria is one of the major tropical diseases afflicting over 300 million and killing about 1 million individuals annually. Majority of the current treatments fo malaria are becoming ineffective because of emergence of drug resistance parasites. Therefore, it is urgent to develop new malaria therapeutics to mitigate this serious problem. The proposed research project seeks to discover novel chemical entities from marine microbes targeting the malaria parasite is timely and will provide entry into novel therapeutic intervention for the disease.
描述(由申请人提供):全世界每年有超过3亿例疟疾临床发作,超过100万例死亡,主要是5岁以下儿童。超过41%的世界人口生活在疟疾传播的地区。疟疾造成的全球经济损失是惊人的。除了对最贫穷国家的总体儿童死亡率有重大贡献外,估计疟疾还导致疟疾负担沉重的国家的经济增长减少约1.3%。不幸的是,目前用于治疗疟疾的大多数药物都是30多年前开发的,其中许多是较老药物的衍生物。由于没有大规模努力开发抗疟疾新药,大多数抗疟疾药物由于广泛的耐药性而变得无效。在发现治疗疟疾的新疗法方面的投资很少,因此推向市场的新疗法的数量也较少。鉴于疟疾的全球死亡人数和耐药性的传播,重要的是要确定新的化学实体,可以开发成治疗耐药性疟疾的疗法。拟议的研究项目旨在从针对疟疾寄生虫的海洋微生物中发现新的化学实体,这是及时的,并将为该疾病提供新的治疗干预措施。我们的方法将是利用港口分支海洋研究所海洋微生物培养物保藏中心(HBMMCC)的化学和生物多样性,作为新的生物活性天然产物的来源。我们将使用SYBR绿色I荧光测定法测定一种新的海洋微生物衍生提取物文库抑制疟原虫生长的能力。将使用液相色谱-质谱(LC-MS)和NMR方法对活性提取物进行去复制,将进一步分析具有最大新化学潜力的那些提取物对一组耐药恶性疟原虫菌株的活性,以确定效力,并分析哺乳动物细胞系,以帮助评估治疗指数。将通过生物测定指导的分级分离来确定生物活性成分的结构,以获得对疟疾寄生虫具有强效力、对哺乳动物细胞具有低毒性和具有新化学性质的提取物。拟议的研究意义重大,因为在该项目结束时,我们预计将有一个抗疟疾“命中”组合 公共卫生相关性:疟疾是主要的热带疾病之一,每年影响3亿多人,造成约100万人死亡。由于抗药性寄生虫的出现,目前大多数疟疾治疗方法变得无效。因此,迫切需要开发新的疟疾疗法来缓解这一严重问题。拟议的研究项目旨在从针对疟疾寄生虫的海洋微生物中发现新的化学实体,这是及时的,并将为该疾病提供新的治疗干预。

项目成果

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DEBOPAM CHAKRABARTI其他文献

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{{ truncateString('DEBOPAM CHAKRABARTI', 18)}}的其他基金

Plasmodium Protein Kinase Focused Antimalarials Discovery
疟原虫蛋白激酶聚焦抗疟药的发现
  • 批准号:
    10533634
  • 财政年份:
    2022
  • 资助金额:
    $ 22.84万
  • 项目类别:
Plasmodium Protein Kinase Focused Antimalarials Discovery
疟原虫蛋白激酶聚焦抗疟药的发现
  • 批准号:
    10663334
  • 财政年份:
    2022
  • 资助金额:
    $ 22.84万
  • 项目类别:
Novel Antimalarials from Fungi
来自真菌的新型抗疟药
  • 批准号:
    10614534
  • 财政年份:
    2020
  • 资助金额:
    $ 22.84万
  • 项目类别:
Novel Antimalarials from Fungi
来自真菌的新型抗疟药
  • 批准号:
    10166769
  • 财政年份:
    2020
  • 资助金额:
    $ 22.84万
  • 项目类别:
Novel Antimalarials from Fungi
来自真菌的新型抗疟药
  • 批准号:
    10388240
  • 财政年份:
    2020
  • 资助金额:
    $ 22.84万
  • 项目类别:
Discovery of Antimalarials with Novel Mechanism of Action
发现具有新颖作用机制的抗疟药
  • 批准号:
    10320854
  • 财政年份:
    2018
  • 资助金额:
    $ 22.84万
  • 项目类别:
Natural Product-Inspired Novel Synthetic Antiplasmodial Scaffolds
天然产物启发的新型合成抗疟原虫支架
  • 批准号:
    8872417
  • 财政年份:
    2015
  • 资助金额:
    $ 22.84万
  • 项目类别:
Novel Antimalarials from Marine Microbial Natural Products
来自海洋微生物天然产物的新型抗疟药
  • 批准号:
    8424201
  • 财政年份:
    2012
  • 资助金额:
    $ 22.84万
  • 项目类别:
Chemical Genetics of Plasmodium Kinases
疟原虫激酶的化学​​遗传学
  • 批准号:
    7879102
  • 财政年份:
    2009
  • 资助金额:
    $ 22.84万
  • 项目类别:
Marine Natural Products as Antimalarials
海洋天然产品作为抗疟药
  • 批准号:
    7589385
  • 财政年份:
    2009
  • 资助金额:
    $ 22.84万
  • 项目类别:

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