Taxuspines A ∼ C, new taxoids from Japanese yew Taxus cuspidata inhibiting drug transport activity of P-glycoprotein in multidrug-resistant cells

Three new taxoids, taxuspines A ∼ C (1 ∼ 3), possessing different skeletons from usual taxane diterpenoids consisting of a 6/8/6-membered ring system have been isolated together with known taxoids (4 ∼ 12) from stems of the Japanese yew Taxus cuspidata Sieb. et Zucc. and the structures elucidated on the basis of spectroscopic data. Most of the taxoids increased cellular accumulation of vincristine in multidrug-resistant tumor cells, while taxol (12) did not show such an activity. The taxoids (1 ∼ 11) showed no or weak cytotoxicity and among them, 2 and 6 reduced appreciably CaCI2-induced depolymerization of microtubules. These results suggest that some taxoids may be useful for overcoming multidrug resistance in tumor cells.