Bioorganic & Medicinal Chemistry Letters 2013-02-01

In vitro efficiency of 9-(N-cinnamoylbutyl)aminoacridines against blood- and liver-stage malaria parasites.

Bianca Pérez, Cátia Teixeira, Ana S Gomes, Inês S Albuquerque, Jiri Gut, Philip J Rosenthal, Miguel Prudêncio, Paula Gomes

Index: Bioorg. Med. Chem. Lett. 23(3) , 610-3, (2013)

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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 μM. Hence, 9-(N-cinnamoylbutyl)aminoacridines are a new class of leads for prevention and treatment of malaria.Copyright © 2012 Elsevier Ltd. All rights reserved.