Novel quinone methides from Salacia kraussii with in vitro antimalarial activity.
Three novel quinone methides, i.e., 28-nor-isoiguesterin-17-carbaldehyde (1), 17-(methoxycarbonyl)-28-nor-isoiguesterin (2), and 28-hydroxyisoiguesterin (3), together with the known celastrol (5), pristimerin (6), and isoiguesterol (7), were isolated from the roots of Salacia kraussii (Celastraceae) by bioassay-guided fractionation. The structures of the compounds were determined by DEPT and 2D NMR techniques. The isolates showed antimalarial activity 30-50-fold greater than their cytotoxicity (in HT-29 cells) in vitro, and they showed an additive effect when combined with each other. In vivo, 2 was found to be inactive against blood stages of Plasmodium berghei in mice after oral and parenteral administration, and the compound was toxic with increasing concentrations.
Figueiredo
J N
JN
Institut für Organische Chemie, Universität Basel, St. Johanns-Ring 19, CH-4056 Basel, Switzerland.
Räz
B
B
Séquin
U
U
D000818:Animals; D000962:Antimalarials / Q000302:isolation & purification* / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology; D002240:Carbohydrate Sequence; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D006801:Humans; D066298:In Vitro Techniques; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D051379:Mice; D008969:Molecular Sequence Data; D010946:Plants, Medicinal / Q000737:chemistry*; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects; D011809:Quinones / Q000302:isolation & purification* / Q000494:pharmacology*; D013019:South Africa; D014407:Tumor Cells, Cultured
D000962:Antimalarials; D000972:Antineoplastic Agents, Phytogenic; D011809:Quinones