New 4-(N-cinnamoylbutyl)aminoacridines as potential multi-stage antiplasmodial leads

卷:258

Article

关键词: CINNAMIC ACID-DERIVATIVES;    PLASMODIUM-FALCIPARUM;    LIVER-STAGE;    MALARIA;    QUINACRINE;    PRIMAQUINE;    ARTEMISININ;    RESISTANCE;    ANALOGS;    AGENTS;   

DOI  :  10.1016/j.ejmech.2023.115575

来源: SCIE

【 摘 要 】

A novel family of 4-aminoacridine derivatives was obtained by linking this heteroaromatic core to different trans-cinnamic acids. The 4-(N-cinnamoylbutyl)aminoacridines obtained exhibited in vitro activity in the low-or sub-micromolar range against (i) hepatic stages of Plasmodium berghei, (ii) erythrocytic forms of Plasmodium falcip-arum, and (iii) early and mature gametocytes of Plasmodium falciparum. The most active compound, having a meta-fluorocinnamoyl group linked to the acridine core, was 20-and 120-fold more potent, respectively, against the hepatic and gametocyte stages of Plasmodium infection than the reference drug, primaquine. Moreover, no cytotoxicity towards mammalian and red blood cells at the concentrations tested was observed for any of the compounds under investigation. These novel conjugates represent promising leads for the development of new multi-target antiplasmodials.

【 授权许可】

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