Targeting the erythrocytic and liver stages of malaria parasites with s-triazine-based hybrids

ChemMedChem
Catarina A B RodriguesRui Moreira

Abstract

A diversity-oriented library of s-triazine-based hybrids was screened for activity against the chloroquine-resistant Plasmodium falciparum W2 strain. The most striking result was sub-micromolar activity against cultured erythrocytic-stage parasites of hybrid molecules containing one or two 8-aminoquinoline moieties. These compounds were not clearly toxic to human cells. The most effective blood-schizontocidal s-triazine derivatives were then screened for activity against the liver stage of malaria parasites. The s-triazine hybrid containing two 8-aminoquinoline moieties and one chlorine atom emerged as the most potent against P. berghei liver-stage infection, active in the low nanomolar region, combined with good metabolic stability in rat liver microsomes. These results indicate that s-triazine-8-aminoquinoline-based hybrids are excellent starting points for lead optimization as dual-stage antimalarials.

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Citations

Jan 19, 2016·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Thabang Mokgethi-Morule, David D N'Da
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Aug 26, 2020·Inorganic Chemistry·Sofia A MilheiroRui Moreira

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