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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:23

Article

Perez, Bianca¹  Teixeira, Catia^1,2  Gomes, Ana S.¹  Albuquerque, Ines S.³  Gut, Jiri⁴  Rosenthal, Philip J.⁴  Prudencio, Miguel³  Gomes, Paula¹ 

[1] Univ Porto, Fac Ciencias, Dept Quim & Bioquim, Ctr Invest Quim, P-4169007 Oporto, Portugal

[2] Univ Aveiro, CICECO, Dept Quim, P-3810193 Aveiro, Portugal

[3] Univ Lisbon, Inst Mol Med, Fac Med, P-1649028 Lisbon, Portugal

[4] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA 94143 USA

关键词: 9-Aminoacridine;    Antimalarials;    Blood-stage;    Cinnamic acid;    Liver-stage;    Multi-target drugs;    Plasmodium falciparum;    Schizontocidal;   

DOI  :  10.1016/j.bmcl.2012.12.032

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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