|
Title
|
|
|
|
Structure-activity relationship of antiparasitic and cytotoxic indoloquinoline alkaloids, and their tricyclic and bicyclic analogues
| |
|
Author
|
|
|
|
| |
|
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-â-carboline, showed the best in vitro activity, with an IC50 value of 0.45 ìM against P. falciparum K1, without apparent cytotoxicity against L6 cells (SI > 1000). However, this compound was not active in the Plasmodium berghei mouse model. Structureactivity relationships are discussed and compared with related naturally occurring compounds. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
Bioorganic and medicinal chemistry. - Oxford
| |
|
Publication
|
|
|
|
Oxford
:
2009
| |
|
ISSN
|
|
|
|
0968-0896
| |
|
DOI
|
|
|
|
10.1016/J.BMC.2009.08.057
| |
|
Volume/pages
|
|
|
|
17
:20
(2009)
, p. 7209-7217
| |
|
ISI
|
|
|
|
000270434000014
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|