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Title
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Structure-activity relationship of antiparasitic and cytotoxic indoloquinoline alkaloids, and their tricyclic and bicyclic analogues
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Bioorganic and medicinal chemistry. - Oxford
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Publication
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Oxford
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2009
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ISSN
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0968-0896
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Volume/pages
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17
:20
(2009)
, p. 7209-7217
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ISI
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000270434000014
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Full text (Publisher's DOI)
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