Intrinsic fluorescence properties of antimalarial pyrido[1,2-a]benzimidazoles facilitate subcellular accumulation and mechanistic studies in the human malaria parasite Plasmodium falciparum.
Intrinsic fluorescence properties of antimalarial pyrido[1,2-a]benzimidazoles facilitate subcellular accumulation and mechanistic studies in the human malaria parasite Plasmodium falciparum.
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抗疟吡啶并[1，2-a]苯并咪唑的内在荧光特性促进了人疟原虫恶性疟原虫的亚细胞积累和机制研究。
DOI：
10.1039/d0ob01730b
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发表时间：
2020-11-04
影响因子：
3.2
通讯作者：
Chibale K
中科院分区：
文献类型：
--
作者：
Korkor CM;Garnie LF;Amod L;Egan TJ;Chibale K
描述了两种相关的吡啶并[1，2-a]苯并咪唑抗疟化合物的固有荧光性质，其适用于人类恶性疟原虫的细胞成像，而不需要附加外部荧光团。虽然这些化合物在结构上是相关的，但共聚焦显微镜显示它们不仅在恶性疟原虫内选择性地积累，而且在所研究的细胞器中也有不同的积累。观察到化合物2定位于消化泡和附近的中性脂质，使用细胞分级分离测定显示化合物2抑制疟原虫色素形成，表明这是一种起作用的机制。相比之下，化合物1与化合物2的不同之处在于咪唑[1，2-a：4，5-b ']联吡啶核被苯并咪唑核取代以及Cl取代基的存在，化合物1显示出非常不同的定位模式，并且没有显示出疟原虫色素抑制的证据，这表明了不同的抗疟作用机制。两种化合物在疟原虫色素表面的对接特征进一步提供了对其作用机制的深入了解。本征荧光性质，对接和疟原虫色素抑制实验研究了两个结构相关的吡啶并[1，2-a]苯并咪唑衍生物的作用机制。
The intrinsic fluorescence properties of two related pyrido[1,2-a]benzimidazole antimalarial compounds suitable for cellular imaging of the human malaria parasite Plasmodium falciparum without the need to attach extrinsic fluorophores are described. Although these compounds are structurally related, they have been shown by confocal microscopy to not only accumulate selectively within P. falciparum but to also accumulate differently in the organelles investigated. Localization to the digestive vacuole and nearby neutral lipids were observed for compound 2 which was shown to inhibit hemozoin formation using a cellular fractionation assay indicating that, this is a contributing mechanism of action. By contrast, compound 1, which differs from compound 2 by the replacement of the imidazole[l,2-a:4,5-b’]dipyridine core with the benzimidazole core as well as the presence of Cl substituents, shows very different localisation patterns and shows no evidence of hemozoin inhibition, suggesting a different mechanism of antimalarial action. Docking profiles of both compounds on the hemozoin surface further provided insight into their mechanisms of action. Intrinsic fluorescence properties, docking and a hemozoin inhibition assay were employed to study the mechanism of action of two structurally related pyrido-[1,2-a]benzimidazole derivatives.
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影响因子：
--
作者：
MELHUISH, WH
通讯作者：
MELHUISH, WH
影响因子：
3.5
作者：
Bantscheff, Marcus;Drewes, Gerard
通讯作者：
Drewes, Gerard
影响因子：
3.8
作者：
Buller, R;Peterson, ML;Leiserowitz, L
通讯作者：
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4
作者：
Gildenhuys, Johandie;Sammy, Chandre J.;de Villiers, Katherine A.
通讯作者：
de Villiers, Katherine A.
影响因子：
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作者：
de Villiers, Katherine A.;Marques, Helder M.;Egan, Timothy J.
通讯作者：
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