Proton- and carbon-13 NMR assignments of phyllanthin and hypophyllanthin: Lignans that enhance cytotoxic responses with cultured multidrug-resistant cells


Somanabandhu, A.; Nitayangkura, S.; Mahidol, C.; Ruchirawat, S.; Likhitwitayawuid, K.; Shieh, H.L.; Chai, H.; Pezzuto, J.M.; Cordell, G.A.

Lloydia 56(2): 233-239

1993


Complete 1H-nmr data and unambiguous assignments of the 13C-nmr spectra of phyllanthin (1) and hypophyllanthin (2) were obtained through extensive nmr studies, including homonuclear COSY, homonuclear decoupling, ATP, 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 venblastine with membrane vesicles derived from this cell line, suggesting an interaction with the P-glycoprotein.