(-)-ROEMERINE, AN APORPHINE ALKALOID FROM ANNONA-SENEGALENSIS THAT REVERSES THE MULTIDRUG-RESISTANCE PHENOTYPE WITH CULTURED-CELLS

A known aporphine alkaloid, (-)-roemerine [1], isolated from the leave s of Annona senegalensis, was found to enhance the cytocoxic response mediated by vinblastine with multidrug-resistant KB-V1 cells. In the a bsence of vinblastine, no significant cytotoxicity was observed with K B-3 or KB-V1 cells (ED(50) > 20 mu g/ml), and several other human tumo r cell lines were also relatively insensitive. As indicated by its abi lity to inhibit ATP-dependent [H-3]vinblastine binding to multidrug-re sistant KB-V1 cell membrane vesicles, (-)-roemerine appears to functio n by interacting with P-glycoprotein. In addition to alkaloid 1, three inactive compounds [the aporphine alkaloid(-)-isocorydine (reported i n the levo-configuration for the first rime), and the lignans (+/-)-8, 8'-bisdihydrosiringenin [2] (a new natural product), and (+)-syringare sinol] were also isolated.