期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 102, 期 4, 页码 699-712出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2007.10.015
关键词
cisplatin-resistance; DNA intercalators; Pt(II); thioureas; ovarian cancer cells
Six bipyridyl complexes of platinum(II) with thiourea, with different substituents on thiourea moiety [Pt(bipy)(R,R'NCSNR '',lR''')(2)]Cl-2 (bipy = 2,2'-bipyridine: R R' = R '' = R' H; R = Me, R' = R '' = R' = H; R = n-Bu, R' = R '' = R' = H; R = Et, R' = H, R '' = Et, R' = H; R = p-tolyl, R' R '' = R ' = H; R = phenyl, R' = H, R '' = phenyl, R' = H), rationally designed to intercalate into DNA, have been tested against a cisplatin (cDDP)-sensitive human ovarian carcinoma cell line (2008) and its-resistant variant (C13*). We show here that the anti-proliferative efficacy of these drugs was dependent on molecular structure, since it increased with ancillary ligand bulkiness and hydrophobicity of substituents on thiourea moiety. In particular, the presence of two phenyl groups on thiourea moiety confers an outstanding cytotoxicity. The increasing cell growth inhibition along the series of complexes partially paralleled with drug accumulation, particularly in resistant cells, but not with drug intercalation into DNA since all compounds exerted comparable ethidium bromide displacement ability. The cDDP-resistant phenotype seems, at least in part, to be involved in the action of these compounds, since the level of cross-resistance established for most complexes appeared to be in agreement with the observed impairment of drug accumulation in the resistant subline. These findings indicate that resistance to alkylating agents such as cDDP confers low level of cross-resistance to this class of DNA intercalators, which, however, depending on substituents on thiourea moiety may present remarkable cell growth inhibition even of resistant cells. (c) 2007 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据