Fungal Metabolite Asperaculane B Inhibits Malaria Infection and Transmission
Fungal Metabolite Asperaculane B Inhibits Malaria Infection and Transmission
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DOI：
10.3390/molecules25133018
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发表时间：
2020-07-01
期刊：
影响因子：
4.6
通讯作者：
Li, Jun
中科院分区：
文献类型：
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作者：
Niu, Guodong;Hao, Yue;Li, Jun
蚊子传播的疟疾寄生虫每年导致全球数百万人罹患疟疾。抗药性疟原虫和抗药性蚊子使疟疾难以控制。因此，需要下一代抑制疟疾感染和传播的抗疟疾药物。我们筛选了我们的全球真菌提取物文库(GFEL)，获得了一个完全抑制恶性疟原虫向冈比亚按蚊传播的候选基因。经鉴定，候选真菌菌株为尖曲霉。对该活性物质进行了纯化，鉴定为阿斯卡林B，50%抑制浓度。恶性疟原虫传播IC50为7.89×10~6×10~(-6)×10~(-6)×10~(-6)×10~(-1)×10~(-1)×10~(-1)×10~(-6)×10~(-6)×10~(-1)×10~(-6)×10~(-6)×10~(-6)×10~(-6)×10~(-1)×10~(-1)×10~(-1)×10~(-6)×10~(-6)×10~(-1)×10~(-1)，对无性疟原虫的发育也有抑制作用。恶性疟原虫IC(50)为3mU M，对人细胞无毒。因此，Aspaculane B是一种新的双功能抗疟疾先导化合物，具有治疗疟疾和阻断疟疾传播的潜力。
Mosquito-transmittedPlasmodiumparasites cause millions of people worldwide to suffer malaria every year. Drug-resistantPlasmodiumparasites and insecticide-resistant mosquitoes make malaria hard to control. Thus, the next generation of antimalarial drugs that inhibit malaria infection and transmission are needed. We screened our Global Fungal Extract Library (GFEL) and obtained a candidate that completely inhibitedPlasmodium falciparumtransmission toAnopheles gambiae. The candidate fungal strain was determined asAspergillus aculeatus. The bioactive compound was purified and identified as asperaculane B. The concentration of 50% inhibition onP. falciparumtransmission (IC50) is 7.89 mu M. Notably, asperaculane B also inhibited the development of asexualP. falciparumwith IC(50)of 3 mu M, and it is nontoxic to human cells. Therefore, asperaculane B is a new dual-functional antimalarial lead that has the potential to treat malaria and block malaria transmission.