1. Academic Validation
  2. Primaquine homodimers as potential antiplasmodial and anticancer agents

Primaquine homodimers as potential antiplasmodial and anticancer agents

  • Bioorg Med Chem Lett. 2019 Oct 1;29(19):126614. doi: 10.1016/j.bmcl.2019.08.018.
Kristina Pavić 1 Barbara Rubinić 1 Zrinka Rajić 1 Diana Fontinha 2 Miguel Prudêncio 2 Lidija Uzelac 3 Marijeta Kralj 3 Jana Held 4 Branka Zorc 5
Affiliations

Affiliations

  • 1 University of Zagreb, Faculty of Pharmacy and Biochemistry, 10000 Zagreb, Croatia.
  • 2 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
  • 3 Laboratory of Experimental Therapy, Division of Molecular Medicine, Rudjer Bošković Institute, 10000 Zagreb, Croatia.
  • 4 University of Tübingen, Institute of Tropical Medicine, 72074 Tübingen, Germany.
  • 5 University of Zagreb, Faculty of Pharmacy and Biochemistry, 10000 Zagreb, Croatia. Electronic address: bzorc@pharma.hr.
Abstract

Primaquine homodimers, e.g. symmetric PQ-diamides of dicarboxylic acids containing 4 to 8 carbon atoms, were evaluated against Plasmodium berghei hepatic stages and P. falciparum blood stages, as well as against three Cancer cell lines. Novel PQ-homodimers exerted much higher activity against hepatic stages, but less pronounced activity against blood stages in comparison to the parent drug. The submicromolar activity of succinic, fumaric and maleic derivatives against P. berghei was determined (IC50 values: 726.2, 198.1 and 358.4 nM, respectively). Our results indicated that the length and type of spacer between two PQ moieties highly modified the antiproliferative activities of PQ-homodimers. The general antiproliferative activity of the adipic and mesaconic derivatives against three Cancer cell lines (MCF-7, HCT116, H 460) was observed (GI50 = 1.78-13.7 and 2.36-4.31 µM, respectively), but adipic derivative was less toxic to human embryonic kidney cells (HEK 293). High selectivity of fumaric and suberic derivatives against breast adenocarcinoma cell line MCF-7 was detected. These two compounds have shown no antiproliferative activity against Other tumor cells and HEK 293.

Keywords

Antiplasmodial activity; Cytostatic activity; Homodimer; Primaquine.

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