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. 2023 Oct 5:258:115575.
doi: 10.1016/j.ejmech.2023.115575. Epub 2023 Jun 22.

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

Mélanie Fonte  1 , Diana Fontinha  2 , Diana Moita  2 , Omar Caño-Prades  3 , Yunuen Avalos-Padilla  3 , Xavier Fernàndez-Busquets  4 , Miguel Prudêncio  2 , Paula Gomes  5 , Cátia Teixeira  6
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Free article

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

Mélanie Fonte et al. Eur J Med Chem. .
Free article

Abstract

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 falciparum, 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.

Keywords: Acridine; Antimalarial; Blood-stage; Cinnamic acid; Gametocyte; Hybrid; Liver-stage; Multi-target.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.