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

Gitte Van Baelen, Steven Hostyn, Liene Dhooghe, P. Tapolcsányi, P. Mátyus, Guy Lemière, Roger Dommisse, Marcel Kaiser, Reto Brun, Paul Cos, Louis Maes, G. Hajós, Z. Riedl, Ildikó Nagy, Bert U W Maes, Luc Pieters

Research output: Contribution to journalArticle

47 Citations (Scopus)

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-β-carboline, showed the best in vitro activity, with an IC50 value of 0.45 μM 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.

Original languageEnglish
Pages (from-to)7209-7217
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number20
DOIs
Publication statusPublished - Oct 15 2009

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Antiparasitic Agents
Carbolines
Structure-Activity Relationship
Alkaloids
Plasmodium falciparum
Lead compounds
Plasmodium berghei
Chloroquine
Antimalarials
Cytotoxicity
Inhibitory Concentration 50
Derivatives

Keywords

  • Antimalarial
  • Antiparasitic
  • Antiplasmodial
  • Azaindole
  • Carboline
  • Cytotoxic
  • Indoloisoquinoline
  • Indoloquinoline alkaloid
  • Pyrroloisoquinoline
  • Pyrroloquinoline

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Structure-activity relationship of antiparasitic and cytotoxic indoloquinoline alkaloids, and their tricyclic and bicyclic analogues. / Van Baelen, Gitte; Hostyn, Steven; Dhooghe, Liene; Tapolcsányi, P.; Mátyus, P.; Lemière, Guy; Dommisse, Roger; Kaiser, Marcel; Brun, Reto; Cos, Paul; Maes, Louis; Hajós, G.; Riedl, Z.; Nagy, Ildikó; Maes, Bert U W; Pieters, Luc.

In: Bioorganic and Medicinal Chemistry, Vol. 17, No. 20, 15.10.2009, p. 7209-7217.

Research output: Contribution to journalArticle

Van Baelen, G, Hostyn, S, Dhooghe, L, Tapolcsányi, P, Mátyus, P, Lemière, G, Dommisse, R, Kaiser, M, Brun, R, Cos, P, Maes, L, Hajós, G, Riedl, Z, Nagy, I, Maes, BUW & Pieters, L 2009, 'Structure-activity relationship of antiparasitic and cytotoxic indoloquinoline alkaloids, and their tricyclic and bicyclic analogues', Bioorganic and Medicinal Chemistry, vol. 17, no. 20, pp. 7209-7217. https://doi.org/10.1016/j.bmc.2009.08.057
Van Baelen, Gitte ; Hostyn, Steven ; Dhooghe, Liene ; Tapolcsányi, P. ; Mátyus, P. ; Lemière, Guy ; Dommisse, Roger ; Kaiser, Marcel ; Brun, Reto ; Cos, Paul ; Maes, Louis ; Hajós, G. ; Riedl, Z. ; Nagy, Ildikó ; Maes, Bert U W ; Pieters, Luc. / Structure-activity relationship of antiparasitic and cytotoxic indoloquinoline alkaloids, and their tricyclic and bicyclic analogues. In: Bioorganic and Medicinal Chemistry. 2009 ; Vol. 17, No. 20. pp. 7209-7217.
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