Evaluation of naphthoquinones identified the acetylated isolapachol as a potent and selective antiplasmodium agent
Diogo RM Moreira, Matheus S de Sa, Tais S Macedo, Maria N Menezes, Jose Rui M Reys, Antonio EG Santana, Thaissa L Silva, Gabriela LA Maia, Jose M Barbosa-Filho, Celso A Camara, Tania MS da Silva, Katia N da Silva, Elisalva T Guimaraes, Ricardo R dos Santos, Marilia OF Goulart, Milena BP Soares
Journal of Enzyme Inhibition and Medicinal Chemistry | TAYLOR & FRANCIS LTD | Published : 2015
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 genoto..View full abstract
This work received fundings from Conselho Nacional de Pesquisas Brasileira (CNPq), Fundacao de Amparo as Pesquisas do Estado da Bahia (FAPESB), Fundacao de Amparo a Pesquisa do Estado de Alagoas (FAPEAL) and Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES). M.B.P.S., M.O.G.S., A.E.G.S., C.A.C., J.M.B.F. and R.R.S hold a CNPq fellowship. T.S.M. is holding a FAPESB doctoral scholarship, while D.R.M.M. is holding a FAPESB scholarship for visiting scholars.