Novel molecule combinations and corresponding hybrids targeting artemisinin-resistant Plasmodium falciparum parasites

Malaria is still considered as the major parasitic disease and development of artemisinin resistance does not improve this alarming situation. Based on recent identification relevant malaria targets in context, novel drug combinations were evaluated against artemisinin-sensitive artemisinin-resistant Plasmodium falciparum parasites. Corresponding hybrid molecules also synthesized for comparison with individual pharmacophores (e.g. atovaquone, mefloquine or triclosan). Combinations hybrids showed remarkable antimalarial activity (IC 50 = 0.6 to 1.1 nM best compounds), strong selectivity, didn’t present any cross-resistance artemisinin. Moreover, combination triclosan + atovaquone high parasites at quiescent stage but corresponding lost pharmacological property. This result essential since only few active are reported. Our promising results highlight potential these paves way pharmacomodulation work hybrids.