Indole alkaloids from Peschiera laeta that enhance vinblastine-mediated cytotoxicity with multidrug-resistant cells.
Coronaridine [1], conoduramine [2], and voacamine [3], three indole alkaloids isolated from Peschiera laeta, have been found to enhance the cytotoxic response mediated by vinblastine [4] with multidrug-resistant KB cells. Inhibition of vinblastine binding with membrane vesicles isolated from this cell line was also assessed, and the bisindole alkaloids conoduramine [2] and voacamine [3] were found to be more potent inhibitory agents than the monomeric alkaloid, coronaridine [1]. Thus, these compounds appear to function by binding with P-glycoprotein.
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Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Illinois 60612.
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Mukherjee
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Farnsworth
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Cordell
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Kinghorn
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Pezzuto
J M
JM
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects*; D018432:Drug Resistance, Multiple; D004357:Drug Synergism; D006801:Humans; D007050:Ibogaine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000633:toxicity; D007624:KB Cells; D014197:Trees; D014747:Vinblastine / Q000633:toxicity*
D000470:Alkaloids; D000970:Antineoplastic Agents; C091978:conoduramine; C005891:voacamine; D007050:Ibogaine; C011734:coronardine; D014747:Vinblastine