Structure-cytotoxic activity relationship for the toad poison bufadienolides.
The toad poison bufadienolides including natural and derivatized compounds were tested for their cytotoxic effects on primary liver carcinoma cells PLC/PRF/5 and their structure-cytotoxic activity relationships were studied. For this study, a ligand-binding model was developed by using a pharmacophore mapping program, Distance Comparisons (DISCO). The structural features that are common to the 3D structures of active bufadienolides were identified to provide approach to a 3D QSAR method by using Comparative Molecular Field Analysis (CoMFA) study and to correlate the steric and electrostatic fields of the molecules to their activities. A valuable model which enables prediction of their activities was obtained from the CoMFA analysis, which may be employed for the drug designs of new bufadienolide analogues.
Kamano
Y
Y
Faculty of Science, Kanagawa University, Hiratsuka, Japan.
Kotake
A
A
Hashima
H
H
Inoue
M
M
Morita
H
H
Takeya
K
K
Itokawa
H
H
Nandachi
N
N
Segawa
T
T
Yukita
A
A
Saitou
K
K
Katsuyama
M
M
Pettit
G R
GR
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002018:Bufanolides / Q000737:chemistry* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000473:pathology; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002018:Bufanolides