ABSTRACT
This study reports on the design, synthesis and antiparasitic activity of three new semi-synthetic naphthoquinones structurally related to the naturally-occurring lapachol and lapachone. Of the compounds tested, 3-(3-methylbut-1-en-1-yl)-1,4-dioxo-1,4-dihydronaphthalen-2-yl acetate (1) was the most active against Plasmodium falciparum among both natural and semi-synthetic naphthoquinones, showing potent and selective activity. Compound 1 was able to reduce the in vitro parasite burden, in vitro parasite cell cycle, as well as the blood parasitemia in Plasmodium berghei-infected mice. More importantly, infection reduction under compound 1-treatment was achieved without exhibiting mouse genotoxicity. Regarding the molecular mechanism of action, this compound inhibited the hemozoin crystal formation in P. falciparum treated cells, and this was further confirmed by observing that it inhibits the ß-hematin polymerization process similarly to chloroquine. Interestingly, this compound did not affect either mitochondria structure or cause DNA fragmentation in parasite treated cells. In conclusion, we identified a semi-synthetic antimalarial naphthoquinone closely related to isolapachol, which had stronger antimalarial activity than lapachol.
Subject(s)
Antimalarials/pharmacology , Naphthoquinones/pharmacology , Plasmodium berghei/drug effects , Plasmodium falciparum/drug effects , Acetylation , Animals , Mice , Mice, Inbred BALB C , Micronucleus TestsABSTRACT
Iridoids and ecdysteroids are found in some genera of the family Verbenaceae. In such cases, they are used as chemotaxonomic markers for the difficult task of taxonomic identification by using morphological characteristics of plants belonging to this family. The present work describes the distribution of ecdysteroids in plants from the genus Vitex from a review of previous work on seventeen Vitex species. In addition, (13)C-NMR data of the main ecdysteroids found in this genus are described. This study attempted to summarize previous research on ecdysteroids distribution in Vitex species with the addition of (13)C-NMR analysis to further refine the characterization of these compounds in the Verbenaceae family.
