Author/Authors :
Yoshiaki Kamano، نويسنده , , Ayano Kotake، نويسنده , , Hirofumi Hashima، نويسنده , , Masuo Inoue، نويسنده , , Hiroshi Morita، نويسنده , , Koichi Takeya، نويسنده , , Hideji Itokawa، نويسنده , , Nobuyo Nandachi، نويسنده , , Toshiaki Segawa، نويسنده , , Ayako Yukita، نويسنده , , Kyoko Saitou، نويسنده , , Mariko Katsuyama، نويسنده , , George R. Pettit، نويسنده ,
Abstract :
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.
