Cryptolepine analogues containing basic aminoalkyl side-chains at C-11: synthesis, antiplasmodial activity, and cytotoxicity.
A series of cryptolepine derivatives has been synthesized through the incorporation of short basic side-chains in the C-11 position of the 10H-indolo[3,2-b]quinoline scaffold. Their antiplasmodial activity was evaluated in vitro against the chloroquine resistant Plasmodium falciparum W2 strain, showing IC(50) values between 22 and 184 nM, while their cytotoxicity was assessed using HUVEC cells, revealing three compounds with a selectivity ratio higher than 10. The most selective of these derivatives, 4d, with a selectivity ratio of 46, was also the least cytotoxic of the series.
Lavrado
João
J
iMed, CECF, Faculty of Pharmacy, University of Lisbon, Av Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
Paulo
Alexandra
A
Gut
Jiri
J
Rosenthal
Philip J
PJ
Moreira
Rui
R
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D020128:Inhibitory Concentration 50; D010963:Plasmodium falciparum / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity
D000962:Antimalarials; D026121:Indole Alkaloids; D011804:Quinolines; C024015:cryptolepine