Novel Antimalarials from Fungi

来自真菌的新型抗疟药

基本信息

  • 批准号:
    10388240
  • 负责人:
  • 金额:
    $ 75.69万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-05-18 至 2025-04-30
  • 项目状态:
    未结题

项目摘要

Malaria still afflicts about half of the world population causing more than 400,000 deaths, mostly children. The global economic toll of malaria is enormous. Most of the drugs that are currently utilized for malaria treatment, including artemisinin-based combination treatments are losing their effectiveness due to widespread emergence of drug resistance. To address the fragility of malaria therapy, we propose to discover novel antimalarial compounds through screening of a library of fungal secondary metabolites. We hypothesize that fungal secondary metabolites, which are underexplored for antimalarial discovery, will provide us with a unique opportunity to investigate medicinally relevant but untapped chemical space for the discovery of novel malaria therapeutics. Premise for this proposal is based on our promising preliminary screen that has identified fungal extracts and pure compounds of fungal origin with potent antiplasmodial activities. To prove this hypothesis, we propose herein to (1) Screen a library of 10,000 extracts derived from diverse fungal species and dereplicate prioritized bioactive extracts to identify and determine structures of selective antiplasmodial compounds that are active against multiple parasite developmental stages; hits will be screened to determine cross-resistance, and killing rate. (2) Active compounds will be prioritized by in vitro physicochemical, in vivo pharmacology and in vivo efficacy studies. (3) Target identification of prioritized hits will be determined by in vitro evolution of resistance followed by whole genome sequencing. Target validation will be conducted by CRISPR/Cas9 mediated genome editing. The research in this endeavor will be conducted through a multidisciplinary collaboration between the laboratories of Debopam Chakrabarti (University of Central Florida), Robert Cichewicz (University of Oklahoma), Kirsten Hanson (University of Texas San Antonio), Elizabeth Winzeler and Jeremiah Momper (University of California San Diego) with combined expertise in natural product chemistry, malaria cell biology, anti-infective discovery, target identification, and validation. This is a highly significant endeavor, as we will discover novel lead compounds with validated targets for therapy against multidrug resistant malaria.
疟疾仍然折磨着世界上大约一半的人口,造成40多万人死亡

项目成果

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DEBOPAM CHAKRABARTI其他文献

DEBOPAM CHAKRABARTI的其他文献

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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:
    $ 75.69万
  • 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:
    $ 75.69万
  • 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:
    $ 75.69万
  • 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:
    $ 75.69万
  • 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:
    $ 75.69万
  • 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:
    $ 75.69万
  • 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:
    8302637
  • 财政年份:
    2012
  • 资助金额:
    $ 75.69万
  • 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:
    $ 75.69万
  • 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:
    $ 75.69万
  • 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:
    $ 75.69万
  • 项目类别:

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对抗未来流行病的抗感染药物的可持续途径。
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