atovaquone

Malaria is still considered as the major parasitic disease and the development of artemisinin resistance does not improve this alarming situation. Based on the recent identification of relevant malaria targets in the artemisinin resistance context, novel drug combinations were evaluated against artemisinin-sensitive and artemisinin-resistant Plasmodium falciparum parasites.

Plasmodium falciparum (P. falciparum) is the main parasite known to cause malaria in humans. The antimalarial drug atovaquone is known to inhibit the Qo-site of the cytochrome bc1 complex of P. falciparum, which ultimately blocks ATP synthesis, leading to cell death. Through the years, mutations of the P. falciparum cytochrome bc1 complex, causing resistance to atovaquone, have emerged.

Atovaquone belongs to a naphthoquinone class of drugs and is used in combination with proguanil (Malarone) for the treatment of acute, uncomplicated malaria caused by Plasmodium falciparum (including chloroquine-resistant P. falciparum/P. vivax). Numerous quinone-derived compounds have attracted considerable attention in the last few decades due to their potential in antimalarial drug discovery.

The natural naphthoquinones lapachol, α- and β-lapachone are found in Bignoniaceous Brazilian plant species of the Tabebuia genus (synonym Handroanthus) and are recognized for diverse bioactivities, including as antimalarial. The aim of the present work was to perform in silico, in vitro and in vivo studies to evaluating the antimalarial potential of these three naphthoquinones in comparison with atovaquone, a synthetic antimalarial.