[Search for new MDR modifier possessing taxane skeleton].
Among new taxoids, taxuspines A-H and J-T, and known taxoids containing taxol and taxol-type compounds with an N-acylphenylisoserine group at C-13 and an oxetane ring at C-4 and C-5 isolated from stems and leaves of the Japanese yew Taxus cuspidata Sieb. et Zucc., two non-taxol-type compounds remarkably reduced CaCl2-induced depolymerization of microtubules. Furthermore, seven non-taxol-type compounds increased cellular accumulation of vincristine in multidrug-resistant(MDR) tumor cells as potent as verapamil, while taxol and taxol-type compounds did not show such an activity. In addition, the non-taxol-type compounds enhancing vincristine accumulation inhibited competitively binding of azidopine to P-glycoprotein. These results suggest that some non-taxol-type taxoids may be useful for overcoming MDR in tumor cells.
Kobayashi
J
J
Faculty of Pharmaceutical Sciences, Hokkaido University.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000737:chemistry / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D013329:Structure-Activity Relationship; D043823:Taxoids; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane