1H- and 13C-nmr assignments of phyllanthin and hypophyllanthin: lignans that enhance cytotoxic responses with cultured multidrug-resistant cells.
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, 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.
Somanabandhu
A
A
Department of Pharmacognosy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Nitayangkura
S
S
Mahidol
C
C
Ruchirawat
S
S
Likhitwitayawuid
K
K
Shieh
H L
HL
Chai
H
H
Pezzuto
J M
JM
Cordell
G A
GA
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004351:Drug Resistance; D004357:Drug Synergism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007624:KB Cells; D007941:Leukemia P388 / Q000188:drug therapy; D017705:Lignans; D008031:Lignin / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D006023:Glycoproteins; D017705:Lignans; C512682:hypophyllanthin; D014747:Vinblastine; D008031:Lignin