| Literature DB >> 19781948 |
Gitte Van Baelen1, Steven Hostyn, Liene Dhooghe, Pál Tapolcsányi, Péter Mátyus, Guy Lemière, Roger Dommisse, Marcel Kaiser, Reto Brun, Paul Cos, Louis Maes, György Hajós, Zsuzsanna Riedl, Ildikó Nagy, Bert U W Maes, Luc Pieters.
Abstract
Based on the indoloquinoline alkaloids cryptolepine (1), neocryptolepine (2), isocryptolepine (3) and isoneocryptolepine (4), used as lead compounds for new antimalarial agents, a series of tricyclic and bicyclic analogues, including carbolines, azaindoles, pyrroloquinolines and pyrroloisoquinolines was synthesized and biologically evaluated. None of the bicyclic compounds was significantly active against the chloroquine-resistant strain Plasmodium falciparum K1, in contrast to the tricyclic derivatives. The tricyclic compound 2-methyl-2H-pyrido[3,4-b]indole (9), or 2-methyl-beta-carboline, showed the best in vitro activity, with an IC(50) value of 0.45 microM against P. falciparum K1, without apparent cytotoxicity against L6 cells (SI>1000). However, this compound was not active in the Plasmodium berghei mouse model. Structure-activity relationships are discussed and compared with related naturally occurring compounds.Entities:
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Year: 2009 PMID： 19781948 DOI： 10.1016/j.bmc.2009.08.057
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641