H-1-NMR AND C-13-NMR ASSIGNMENTS OF PHYLLANTHIN AND HYPOPHYLLANTHIN - LIGNANS THAT ENHANCE CYTOTOXIC RESPONSES WITH CULTURED MULTIDRUG-RESISTANT CELLS

Complete H-1-nmr data and unambiguous assignments of the C-13-nmr spectra of phyllanthin [1] and hypophyllanthin [2] were obtained through extensive nmr studies, including homonuclear COSY, homonuclear decoupling, APT, HETCOR, nOe difference, selective INEPT, and COLOC experiments. The absolute configuration of hypophyllanthin [2] was determined by cd. Neither of these lignans demonstrated significant cytotoxic activity when evaluated with a battery of cultured mammalian cells, but both were found to enhance the cytotoxic response mediated by vinblastine with multidrug-resistant KB cells. In addition, 1 was found to displace the binding of vinblastine with membrane vesicles derived from this cell line, suggesting an interaction with the P-glycoprotein.