title: Structure-cytotoxic activity relationship for the toad poison bufadienolides.
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.
authors.affiliation: Faculty of Science, Kanagawa University, Hiratsuka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kamano
authors.forename: A
authors.initials: A
authors.lastname: Kotake
authors.forename: H
authors.initials: H
authors.lastname: Hashima
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: H
authors.initials: H
authors.lastname: Morita
authors.forename: K
authors.initials: K
authors.lastname: Takeya
authors.forename: H
authors.initials: H
authors.lastname: Itokawa
authors.forename: N
authors.initials: N
authors.lastname: Nandachi
authors.forename: T
authors.initials: T
authors.lastname: Segawa
authors.forename: A
authors.initials: A
authors.lastname: Yukita
authors.forename: K
authors.initials: K
authors.lastname: Saitou
authors.forename: M
authors.initials: M
authors.lastname: Katsuyama
authors.forename: G R
authors.initials: GR
authors.lastname: Pettit
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D002018:Bufanolides