RRC ID 39234
著者 Kageyama Y, Yamazaki Y, Okuno H.
タイトル Novel approaches to prodrugs of anticancer diaminodichloroplatinum(II) complexes activated by stereoselective enzymatic ester hydrolysis.
ジャーナル J Inorg Biochem
Abstract A series of dichloro(ethylenediamine)-type platinum complexes bearing ester-, amide- and ether-bonded alkyl straight chains (C2-C18) was prepared as a model for the prodrug of cis-diamminedichloroplatinum (CDDP). Evaluation of cytotoxic activity of the complexes against the S-180 cell line proved that their enzymatic hydrolysis in the cells lowered the permeability to the cell membranes resulting in an increase of pharmacological activity. Optically active isomers of dichloro(N-2(2-phenylpropanoyloxy)ethyl)-2,3-diaminopropanamide )platinum(II) were prepared. They were re-activated stereoselectively, and a tenfold difference in activity was observed based on the differences in chiral discrimination by enzymes.
巻・号 70(1)
ページ 25-32
公開日 1998-4-1
DOI 10.1016/s0162-0134(98)00009-9
PII S0162-0134(98)00009-9
PMID 9661285
MeSH Animals Antineoplastic Agents / chemistry Antineoplastic Agents / metabolism* Antineoplastic Agents / therapeutic use Cell Membrane Permeability / drug effects Cisplatin / analogs & derivatives* Cisplatin / metabolism Cisplatin / therapeutic use Hydrolysis Liver Neoplasms, Experimental / drug therapy Liver Neoplasms, Experimental / metabolism Magnetic Resonance Spectroscopy Prodrugs / chemistry Prodrugs / metabolism* Prodrugs / therapeutic use Rats Sarcoma 180 / drug therapy Sarcoma 180 / metabolism Stereoisomerism Tumor Cells, Cultured
IF 3.212
引用数 13
WOS 分野 CHEMISTRY, INORGANIC & NUCLEAR BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 Anr4(RCB0449)