abstract
Novel 9-aminoacridine derivatives were synthesized by linking the heteroaromatic core to different cinnamic acids through an aminobutyl chain. The test compounds demonstrated mid-nanomolar in vitro activity against erythrocytic stages of the chloroquine-resistant W2 strain of the human malaria parasite Plasmodium falciparum. Two of the most active derivatives also showed in vitro activity against liver-stage Plasmodium berghei, with activity greater than that of the reference liver-stage antimalarial primaquine. The compounds were not toxic to human hepatoma cells at concentrations up to 5 mu M. Hence, 9-(N-cinnamoylbutyl)aminoacridines are a new class of leads for prevention and treatment of malaria. (c) 2012 Elsevier Ltd. All rights reserved.
keywords
RESISTANT PLASMODIUM-FALCIPARUM; CHLOROQUINE; DISCOVERY; LEADS
subject category
Pharmacology & Pharmacy; Chemistry
authors
Perez, B; Teixeira, C; Gomes, AS; Albuquerque, IS; Gut, J; Rosenthal, PJ; Prudencio, M; Gomes, P
our authors
Cátia Teixeira
Post-doc FellowshipGroups
Projects
acknowledgements
This project was co-funded by FEDER through the POFC-COMPETE programme (FCOMP-01-0124-FEDER-020963) and by Portuguese national funds through Fundacao para a Ciencia e a Tecnologia (PTDC/QUI-QUI/116864/2010). Funding through project PTDC/SAU-MII/099118/2008 (MP), and strategic projects PEst-C/QUI/UI0081/2011 (PG) and PEst-C/CTM/LA0011/2011 (JRBG) is also acknowledged to Fundacao para a Ciencia e Tecnologia (FCT). C.T. and JRBG thank FCT for the post-doctoral fellowship SFRH/BPD/62967/2009 and for Programa Ciencia 2007, respectively. P.J.R. is a Doris Duke Charitable Foundation Distinguished Clinical Scientist.