Identification of the Schistosoma mansoni Molecular Target for the Antimalarial Drug Artemether

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• 作者：Rosalba Lepore ; Silvia Simeoni ; Domenico Raimondo ; Antonia Caroli ; Anna Tramontano ; Allegra Via
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2011
• 出版时间：November 28, 2011
• 年：2011
• 卷：51
• 期：11
• 页码：3005-3016
• 全文大小：1605K
• 年卷期：v.51,no.11(November 28, 2011)
• ISSN：1549-960X

文摘

Plasmodium falciparum and Schistosoma mansonii are the parasites responsible for most of the malaria and schistosomiasis cases in the world. Notwithstanding their many differences, the two agents have striking similarities in that they both are blood feeders and are targets of an overlapping set of drugs, including the well-known artemether molecule. Here we explore the possibility of using the known information about the mode of action of artemether in Plasmodium to identify the molecular target of the drug in Schistosoma and provide evidence that artemether binds to SmSERCA, a putative Ca²⁺-ATPase of Schistosoma. We also predict the putative binding mode of the molecule for both its Plasmodium and Schistosoma targets. Our analysis of the mode of binding of artemether to Ca²⁺-ATPases also provides an explanation for the apparent paradox that, although the molecule has no side effect in humans, it has been shown to possess antitumoral activity.