Actions of Camptothecin Derivatives on Larvae and Adults of the Arboviral Vector Aedes aegypti.
Actions of Camptothecin Derivatives on Larvae and Adults of the Arboviral Vector Aedes aegypti.
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DOI：
10.3390/molecules26206226
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发表时间：
2021-10-15
期刊：
影响因子：
--
通讯作者：
Sattelle DB
中科院分区：
文献类型：
--
作者：
Partridge FA;Poulton BC;Lake MAI;Lees RA;Mann HJ;Lycett GJ;Sattelle DB
登革热、寨卡病毒和基孔肯雅病毒等蚊媒病毒以及疟疾和盘尾丝虫等寄生虫威胁着全球的健康和经济安全，新出现的蚊媒病原体具有大流行的潜力。然而，杀虫剂抗药性的迅速蔓延威胁到我们控制蚊虫媒介的能力。利用开放源化合物库“Medicines for Malaria Venture Pandemic Response Box”对埃及伊蚊幼虫进行筛选，并利用适用于幼虫动态高通量化学筛选的无脊椎动物自动表型平台INVAPP对埃及伊蚊幼虫进行筛选。我们发现rubitecan（喜树碱的合成衍生物）是一种降低埃及伊蚊幼虫运动能力的有效化合物。rubitecan和喜树碱均显示出浓度依赖性的幼虫活力降低，EC50分别为25.5±5.0µM和22.3±5.4µM。我们将研究扩展到成蚊，发现喜树碱在100µM和10µM的浓度下以血粉形式喂给埃及伊蚊，可提高其致死性，在100µM的浓度下喂给埃及伊蚊，可完全阻断产卵。喜树碱及其衍生物是拓扑异构酶I的抑制剂，已知对几种农业害虫有活性，也被批准用于治疗几种癌症。至关重要的是，它们可以抑制寨卡病毒在人类细胞中的复制，因此有可能双重靶向这种载体及其携带的一种重要虫媒病毒。
Mosquito-borne viruses including dengue, Zika, and Chikungunya viruses, and parasites such as malaria and Onchocerca volvulus endanger health and economic security around the globe, and emerging mosquito-borne pathogens have pandemic potential. However, the rapid spread of insecticide resistance threatens our ability to control mosquito vectors. Larvae of Aedes aegypti were screened with the Medicines for Malaria Venture Pandemic Response Box, an open-source compound library, using INVAPP, an invertebrate automated phenotyping platform suited to high-throughput chemical screening of larval motility. We identified rubitecan (a synthetic derivative of camptothecin) as a hit compound that reduced A. aegypti larval motility. Both rubitecan and camptothecin displayed concentration dependent reduction in larval motility with estimated EC50 of 25.5 ± 5.0 µM and 22.3 ± 5.4 µM, respectively. We extended our investigation to adult mosquitoes and found that camptothecin increased lethality when delivered in a blood meal to A. aegypti adults at 100 µM and 10 µM, and completely blocked egg laying when fed at 100 µM. Camptothecin and its derivatives are inhibitors of topoisomerase I, have known activity against several agricultural pests, and are also approved for the treatment of several cancers. Crucially, they can inhibit Zika virus replication in human cells, so there is potential for dual targeting of both the vector and an important arbovirus that it carries.
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影响因子：
3.8
作者：
Buckingham SD;Partridge FA;Poulton BC;Miller BS;McKendry RA;Lycett GJ;Sattelle DB
通讯作者：
Sattelle DB
DOI：
10.1016/j.gpb.2020.06.016
发表时间：
2021-03
期刊：
Genomics, proteomics & bioinformatics
影响因子：
--
作者：
Song G;Lee EM;Pan J;Xu M;Rho HS;Cheng Y;Whitt N;Yang S;Kouznetsova J;Klumpp-Thomas C;Michael SG;Moore C;Yoon KJ;Christian KM;Simeonov A;Huang W;Xia M;Huang R;Lal-Nag M;Tang H;Zheng W;Qian J;Song H;Ming GL;Zhu H
通讯作者：
Zhu H
DOI：
10.1016/s0140-6736(15)00417-1
发表时间：
2016-04-23
期刊：
Lancet (London, England)
影响因子：
--
作者：
Hemingway J;Ranson H;Magill A;Kolaczinski J;Fornadel C;Gimnig J;Coetzee M;Simard F;Roch DK;Hinzoumbe CK;Pickett J;Schellenberg D;Gething P;Hoppé M;Hamon N
通讯作者：
Hamon N
类视钉X受体的拮抗剂可在体外降低毛尿症的生存能力。
影响因子：
3.7
作者：
Hurst RJ;Hopwood T;Gallagher AL;Partridge FA;Burgis T;Sattelle DB;Else KJ
通讯作者：
Else KJ
DOI：
10.1016/s0140-6736(18)32335-3
发表时间：
2018-11-10
期刊：
Lancet (London, England)
影响因子：
--
作者：
GBD 2017 DALYs and HALE Collaborators
通讯作者：
GBD 2017 DALYs and HALE Collaborators