Isoneocryptolepine, a synthetic indoloquinoline alkaloid, as an antiplasmodial lead compound.
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.
Van Miert
Sabine
S
Department of Pharmaceutical Sciences, University of Antwerp, Belgium.
Hostyn
Steven
S
Maes
Bert U W
BU
Cimanga
Kanyanga
K
Brun
Reto
R
Kaiser
Marcel
M
Mátyus
Péter
P
Dommisse
Roger
R
Lemière
Guy
G
Vlietinck
Arnold
A
Pieters
Luc
L
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
D000470:Alkaloids; D000962:Antimalarials; D026121:Indole Alkaloids; D007211:Indoles; D011804:Quinolines; C501476:isoneocryptolepine; C414982:neocryptolepine; C024015:cryptolepine