Factor analysis of in vitro antitumor activities of platinum complexes.
Factor analysis was applied to the data matrix of in vitro growth inhibitory activities of 52 platinum complexes against 9 tumor cell lines, L1210, P388, Lewis lung, AH66, AH66F, HeLa S3, KB, HT-1197 and HT-1376 cell lines. Three factors were obtained by the principal factor analysis method. After the varimax rotation of these three factors, tumor cell lines were classified into four groups according to their factor loadings. The platinum complexes were characterized by the factor scores. Cisplatin was situated in an extreme position as compared with the other platinum complexes. In vivo antitumor activities of the platinum complexes were tested against L1210 and LL murine tumor models. The in vivo activity against L1210 showed a negative correlation with that against LL. Factor 2 scores of the complexes obtained by factor analysis of in vitro antitumor activities showed a good correlation with these in vivo antitumor activities. Then, the structure-factor 2 score relationships among platinum complexes were analyzed by the Free-Wilson method. From this analysis, structure-activity relationships for carrier ligands and leaving groups are proposed. Factor analysis is suggested to be a useful method to establish an efficient screening system for platinum complexes.
Kuramochi
H
H
Research Laboratories, Nippon Kayaku Co., Ltd., Tokyo, Japan.
Motegi
A
A
Maruyama
S
S
Okamoto
K
K
Takahashi
K
K
Kogawa
O
O
Nowatari
H
H
Hayami
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds