title: Cryptolepine analogues containing basic aminoalkyl side-chains at C-11: synthesis, antiplasmodial activity, and cytotoxicity.
abstract: 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.
authors.affiliation: iMed, CECF, Faculty of Pharmacy, University of Lisbon, Av Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Lavrado
authors.forename: Alexandra
authors.initials: A
authors.lastname: Paulo
authors.forename: Jiri
authors.initials: J
authors.lastname: Gut
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Rui
authors.initials: R
authors.lastname: Moreira
mesh_terms: 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
chemical_list: D000962:Antimalarials; D026121:Indole Alkaloids; D011804:Quinolines; C024015:cryptolepine