Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies

Abstract

Due to the recent advances of atovaquone, a naphthoquinone, through clinical trials as treatment for malarial infection, 19 quinone derivatives with previously reported structures were also evaluated for blood schizonticide activity against the malaria parasite Plasmodium falciparum. These compounds include 2-hydroxy-3-methylamino naphthoquinones (2-9), lapachol (10), nor-lapachol (11), iso-lapachol (12), phthiocol (13) and phenazines (12-20). Their cytotoxicities were also evaluated against human hepatoma and normal monkey kidney cell lines. Compounds 2 and 5 showed the highest activity against P. falciparum chloroquine-resistant blood-stage parasites (clone W2), indicated by their low inhibitory concentration for 50% (IC50) of parasite growth. The therapeutic potential of the active compounds was evaluated according to the selectivity index, which is a ratio of the cytotoxicity minimum lethal dose which eliminates 50% of cells and the in vitro IC50. Naphthoquinones 2 and 5, with activities similar to the reference antimalarial chloroquine, were also active against malaria in mice and suppressed parasitaemia by more than 60% in contrast to compound 11 which was inactive. Based on their in vitro and in vivo activities, compounds 2 and 5 are considered promising molecules for antimalarial treatment and warrant further study.

Ruthenium(II)‐Catalyzed C–H Alkenylation of Quinones: Diversity‐Oriented Strategy for Trypanocidal Compounds

“…The compounds obtained by our new method are structurally similar to the naphthoquinones that we, and others, have synthesized and evaluated during the last few years against clinical targets, such as cancer, malaria, leishmania and tuberculosis, i.e. diseases with an inherently disturbed intracellular redox‐balance.…”

New peptide derived antimalaria and antimicrobial agents bearing sulphonamide moiety

“…The percentage inhibition of parasite multiplication was calculated comparing the treated group with untreated group by means of the following formula 39 [(A − B)/A] × 100; where A = parasitaemia in the untreated group and B = parasitemia in the test group. Compounds that reduced parasitemia by 40% were considered active, whereas those that reduce parasitaemia by 30–40% or less than 30% were deemed partially active and inactive, respectively 40 . Most of the compounds were active against P. berghei after 7 days post-infection by reducing the parasiteamia by at least 40% when in a dose of 100 mg/kg (Table 5).…”

In vitro antiplasmodial activity, pharmacokinetic profiles and interference in isoprenoid pathway of 2-aniline-3-hydroxy-1.4-naphthoquinone derivatives

“…The phenylpiperazine is attached to a piperazine phenylaniline, showing similarity with radicals used in structural changes, as in the present study, which is aniline derivatives and associated with the effectiveness of that radical. In another study, eight derivatives of 2-hydroxy-3-methylamino-1.4-naphthoquinone were tested, and five were active, exhibiting IC 50 values less than 30 μM against P. falciparum W2 (chloroquine-resistant strain) [10].…”

“…The antiparasitic activity of hydroxy-naphthoquinones derivatives is already known, with studies confirming its efficacy against Leishmania braziliensis and Leishmania amazonensis [4], Trypanosoma cruzi [5] and P. falciparum [6–10]. Its mechanism of action was already proposed by means of the inhibition of the mitochondrial electron carrier chain [11].…”