2. Academic Validation
  3. Structure-activity relationship of antiparasitic and cytotoxic indoloquinoline alkaloids, and their tricyclic and bicyclic analogues

Structure-activity relationship of antiparasitic and cytotoxic indoloquinoline alkaloids, and their tricyclic and bicyclic analogues

  • Bioorg Med Chem. 2009 Oct 15;17(20):7209-17. doi: 10.1016/j.bmc.2009.08.057.
Gitte Van Baelen 1,  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
Affiliations

Affiliation

  • 1 Laboratory of Organic Synthesis, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
PMID: 19781948 DOI: 10.1016/j.bmc.2009.08.057
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.

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