2. Academic Validation
  3. New 4-(N-cinnamoylbutyl)aminoacridines as potential multi-stage antiplasmodial leads

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

  • Eur J Med Chem. 2023 Oct 5;258:115575. doi: 10.1016/j.ejmech.2023.115575.
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
Affiliations

Affiliations

  • 1 LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Portugal. Electronic address: up201305020@edu.fc.up.pt.
  • 2 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal.
  • 3 Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Barcelona, Spain.
  • 4 Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Barcelona, Spain; Barcelona Institute for Global Health (ISGlobal, Hospital Clínic-Universitat de Barcelona), Spain; Nanoscience and Nanotechnology Institute (IN2UB), University of Barcelona, Spain.
  • 5 LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Portugal. Electronic address: pgomes@fc.up.pt.
  • 6 LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Portugal; Gyros Protein Technologies Inc., Tucson, AZ, USA.
PMID: 37390511 DOI: 10.1016/j.ejmech.2023.115575
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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