title: Isoneocryptolepine, a synthetic indoloquinoline alkaloid, as an antiplasmodial lead compound.
abstract: The antiprotozoal activities of three naturally occurring isomeric indoloquinoline alkaloids, i.e., cryptolepine (1), neocryptolepine (2), and isocryptolepine (3), and two dimeric indoloquinoline alkaloids, cryptoquindoline (6) and biscryptolepine (7), originally obtained from the plant Cryptolepis sanguinolenta, were compared with those of a new synthetic indoloquinoline isomer, isoneocryptolepine (4), and a quaternary derivative, N-methyl-isocryptolepinium iodide (5). The latter compounds showed a high antiplasmodial activity against the chloroquine-resistant Plasmodium falciparum strain K1 (IC50 of 0.23 +/- 0.04 and 0.017 +/- 0.004 microM, respectively), while the cytotoxicity (L6 cells) was 4.32 +/- 0.04 and 12.7 +/- 2.0 microM, respectively. Isoneocryptolepine (4) was found to act as an inhibitor of beta-hematin formation and as a DNA-intercalating agent.
authors.affiliation: Department of Pharmaceutical Sciences, University of Antwerp, Belgium.
authors.forename: Sabine
authors.initials: S
authors.lastname: Van Miert
authors.forename: Steven
authors.initials: S
authors.lastname: Hostyn
authors.forename: Bert U W
authors.initials: BU
authors.lastname: Maes
authors.forename: Kanyanga
authors.initials: K
authors.lastname: Cimanga
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.forename: Péter
authors.initials: P
authors.lastname: Mátyus
authors.forename: Roger
authors.initials: R
authors.lastname: Dommisse
authors.forename: Guy
authors.initials: G
authors.lastname: Lemière
authors.forename: Arnold
authors.initials: A
authors.lastname: Vlietinck
authors.forename: Luc
authors.initials: L
authors.lastname: Pieters
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D029062:Apocynaceae / Q000737:chemistry; D026121:Indole Alkaloids; D007211:Indoles / Q000494:pharmacology; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D000962:Antimalarials; D026121:Indole Alkaloids; D007211:Indoles; D011804:Quinolines; C501476:isoneocryptolepine; C414982:neocryptolepine; C024015:cryptolepine