Novel Selective Inhibitors of the Zinc Plasmodial Aminopeptidase PfA-M1 as Potential Antimalarial Agents - Archive ouverte HAL Access content directly
Journal Articles Journal of Medicinal Chemistry Year : 2007

Novel Selective Inhibitors of the Zinc Plasmodial Aminopeptidase PfA-M1 as Potential Antimalarial Agents

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Abstract

Proteases that are expressed during the erythocytic stage of Plasmodium falciparum are newly explored drug targets for the treatment of malaria. We report here the discovery of potent inhibitors of PfA-M1, a metallo-aminopeptidase of the parasite. These compounds are based on a malonic hydroxamic template and present a very good selectivity toward neutral aminopeptidase (APN-CD13), a related protease in mammals. Structure-activity relationships in these series are described. Further optimization of the best inhibitor yielded a nanomolar, selective inhibitor of PfA-M1. This inhibitor displays good physicochemical and pharmacokinetic properties and a promising antimalarial activity.

Dates and versions

mnhn-02904302 , version 1 (02-12-2022)

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Marion Flipo, Terence Beghyn, Virginie Leroux, Isabelle Florent, Benoit Déprez, et al.. Novel Selective Inhibitors of the Zinc Plasmodial Aminopeptidase PfA-M1 as Potential Antimalarial Agents. Journal of Medicinal Chemistry, 2007, 50 (6), pp.1322-1334. ⟨10.1021/jm061169b⟩. ⟨mnhn-02904302⟩
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