Authors: De Souza, M.V.N.; Cunico, W.; Cechinel, C.A.; Bonacorso, H.G.; Martins, M.A.P.; Zanatta, N.; Soares, R.P.P.; Krettli, A.U.
Source: Bioorganic & Medicinal Chemistry Letters, v. 16, p. 649-653, 2006.
Publisher: Elsevier
Abstract
The antimalarial activity of chloroquine-pyrazole analogues, synthesized from the reaction of 1,1,1-trifluoro-4-methoxy-3-alken-2-ones with 4-hydrazino-7-chloroquinoline, has been evaluated in vitro against a chloroquine resistant Plasmodium falciparum clone. Parasite growth in the presence of the test drugs was measured by incorporation of [3H]hypoxanthine in comparison to controls with no drugs. All but one of the eight (4,5-dihydropyrazol-1-yl) chloroquine 2 derivatives tested showed a significant activity in vitro, thus, are a promising new class of antimalarials. The three most active ones were also tested in vivo against Plasmodium berghei in mice. However, the (pyrazol-1-yl) chloroquine 3 derivatives were mostly inactive, suggesting that the aromatic functionality of the pyrazole ring was critical.Keywords: Antimalarial; 4,5-Dihydropyrazole; Chloroquine analogues Document Type: Research Article DOI: http://dx.doi.org/10.1016/j.bmcl.2005.10.033 Publication date: 1 de Fevereiro de 2006
