Identifying inhibitors of β-haematin formation with activity against chloroquine-resistant Plasmodium falciparum malaria parasites via virtual screening approaches.
Identifying inhibitors of β-haematin formation with activity against chloroquine-resistant Plasmodium falciparum malaria parasites via virtual screening approaches.
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DOI：
10.1038/s41598-023-29273-w
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发表时间：
2023-02-14
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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作者：
生物矿物色素，或其合成类似物β-血红素（βH），一直是几个针对恶性疟原虫寄生虫活性的靶向筛选的焦点。与已知的βH晶体结构一起，该筛选数据的可用性使得靶标适合于基于结构和基于配体的虚拟筛选。在这项研究中，分子对接和机器学习技术，包括贝叶斯和支持向量机分类器，依次用于筛选计算机模拟ChemDiv 300 k代表性化合物库中对恶性疟原虫具有保留活性的βH抑制剂。我们从商业上获得并测试了一组优先的抑制剂，并将香豆素和亚氨基二吡啶并嘧啶化学型鉴定为βH和全细胞寄生虫生长的有效体外抑制剂。
The biomineral haemozoin, or its synthetic analogue β-haematin (βH), has been the focus of several target-based screens for activity against Plasmodium falciparum parasites. Together with the known βH crystal structure, the availability of this screening data makes the target amenable to both structure-based and ligand-based virtual screening. In this study, molecular docking and machine learning techniques, including Bayesian and support vector machine classifiers, were used in sequence to screen the in silico ChemDiv 300k Representative Compounds library for inhibitors of βH with retained activity against P. falciparum. We commercially obtained and tested a prioritised set of inhibitors and identified the coumarin and iminodipyridinopyrimidine chemotypes as potent in vitro inhibitors of βH and whole cell parasite growth.
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影响因子：
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影响因子：
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作者：
Ncokazi, KK;Egan, TJ
通讯作者：
Egan, TJ
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Leiserowitz, L
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通讯作者：
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