当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Antiproliferative effect of novel platinum(II) and palladium(II) complexes on hepatic tumor stem cells in vitro.

Antiproliferative effect of novel platinum(II) and palladium(II) complexes on hepatic tumor stem cells in vitro.

Abstract：

:Novel platinum and palladium complexes with (2-isopropoxyphenyl)dicyclohexylarsine and (2-methoxyphenyl)dicyclohexylarsine ligands were synthesized and tested on different tumor cells. Adducts with general formula MX(2)L(2) (M = Pt(II), Pd(II); X = Cl or I; L = organoarsenic ligand) were fully characterized. According to the crystallographic data, in all complexes the organoarsenic ligands coordinate the metal center through the arsenic atom only, in a trans arrangement with the halogen atoms. The antiproliferative potential of complexes 1-4 was evaluated in vitro on human tumor cell lines. A markedly biological activity was observed against the chemoresistant hepatic tumor stem cell line, the normal hepatic stem cells and towards the hepatocellular carcinoma (non-stem) cells. The new compounds toxicity is selectively limited in normal liver cells, unlikeness with the oxaliplatin, which displays a more intense effect in normal cells, compared with the two tumor cell lines. The stem cells treatment with compounds 1-4 causes DNA damages; the antimitotic effect of these compounds is based on their genotoxicity and on the capacity to form crosslinks with the DNA interstrand. In the case of platinum complexes 1 and 3 this mechanism gives rise to specific lesions on DNA that induces apoptosis in stem cells, influencing their selectivity in tumor cell growth inhibition. Compounds 1, 2 and 4 display higher activity against tumor stem cells. The novel platinum complexes 1 and 3 are more efficient against tumor stem cells than oxaliplatin, and if used in combination with sorafenib-based monoclonal anticancer therapy, complexes 1, 3 and 4 have the ability to induce superior chemosensitivity relative to sorafenib than the standard platinum-based drug, making them promising candidates for prodrug development.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Miklášová N,Fischer-Fodor E,Lönnecke P,Tomuleasa CI,Virag P,Schrepler MP,Mikláš R,Dumitrescu LS,Hey-Hawkins E

doi

10.1016/j.ejmech.2011.12.001

subject

Has Abstract

pub_date

2012-03-01 00:00:00

pages

41-7

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(11)00864-6

journal_volume

49

pub_type

杂志文章

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