title: Identification of a novel cardenolide (2''-oxovoruscharin) from Calotropis procera and the hemisynthesis of novel derivatives displaying potent in vitro antitumor activities and high in vivo tolerance: structure-activity relationship analyses.
abstract: Analysis of the methanolic extract of Calotropis procera root barks enabled the identification of a novel cardenolide (2''-oxovoruscharin) to be made. Of the 27 compounds that we hemisynthesized, one (23) exhibited a very interesting profile with respect to its hemisynthetic chemical yield, its in vitro antitumor activity, its in vitro inhibitory influence on the Na+/K+-ATPase activity, and its in vivo tolerance. Compound 23 displayed in vitro antitumor activity on a panel of 57 human cancer cell lines similar to taxol, and higher than SN-38 (the active metabolite of irinotecan), two of the most potent drugs used in hospitals to combat cancer.
authors.affiliation: Unibioscreen SA, 40 avenue Joseph Wybran, 1070 Brussels, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Van Quaquebeke
authors.forename: Gentiane
authors.initials: G
authors.lastname: Simon
authors.forename: Aurélie
authors.initials: A
authors.lastname: André
authors.forename: Janique
authors.initials: J
authors.lastname: Dewelle
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Yazidi
authors.forename: Frederic
authors.initials: F
authors.lastname: Bruyneel
authors.forename: Jerome
authors.initials: J
authors.lastname: Tuti
authors.forename: Odile
authors.initials: O
authors.lastname: Nacoulma
authors.forename: Pierre
authors.initials: P
authors.lastname: Guissou
authors.forename: Christine
authors.initials: C
authors.lastname: Decaestecker
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Braekman
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
authors.forename: Francis
authors.initials: F
authors.lastname: Darro
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000302:isolation & purification* / Q000494:pharmacology; D031107:Calotropis / Q000737:chemistry*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002298:Cardenolides / Q000138:chemical synthesis* / Q000302:isolation & purification* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002540:Cerebral Cortex / Q000737:chemistry; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D000077146:Irinotecan; D009682:Magnetic Resonance Spectroscopy; D020714:Maximum Tolerated Dose; D051379:Mice; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D017239:Paclitaxel / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry; D013329:Structure-Activity Relationship; D013552:Swine; D013844:Thiazoles / Q000138:chemical synthesis* / Q000302:isolation & purification* / Q000494:pharmacology
chemical_list: C497151:2''-oxovoruscharin; D000970:Antineoplastic Agents; D002298:Cardenolides; D009944:Organoplatinum Compounds; D013844:Thiazoles; D000077150:Oxaliplatin; D005047:Etoposide; D000077146:Irinotecan; D000254:Sodium-Potassium-Exchanging ATPase; D017239:Paclitaxel; D002166:Camptothecin