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Cytotoxic Triosmium Carbonyl Clusters: A Structure–Activity Relationship Study
Author(s) -
Lee Hui Zhi Shirley,
Leong Weng Kee,
Top Siden,
Vessières Anne
Publication year - 2014
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201300394
Subject(s) - osmium , chemistry , cationic polymerization , cytotoxicity , apoptosis , stereochemistry , cluster (spacecraft) , in vitro , cytotoxic t cell , structure–activity relationship , estrogen receptor , breast cancer , cancer , cancer research , biochemistry , biology , ruthenium , organic chemistry , computer science , genetics , programming language , catalysis
Abstract A structure–activity relationship (SAR) study of the triosmium carbonyl cluster Os 3 (CO) 10 (NCCH 3 ) 2 was carried out with a series of clusters of the general formula Os 3 (CO) 12− n L n , cationic osmium clusters and a hemi‐labile maltolato‐Os cluster. The SAR results showed that good solubility in DMSO and at least one vacant site are required for cytotoxicity. In vitro evaluation of these new compounds showed that some are selectively active against estrogen receptor (ER)‐independent MDA‐MB‐231 breast cancer cell lines relative to ER‐dependent MCF‐7 breast cancer cells, suggesting that the compounds have a different biological target specific to MDA‐MB‐231 cells. In particular, the maltolato cluster exhibits strong antiproliferative activity, with an IC 50 value of 3 μ M after only 24 h incubation. Additionally, biochemical assays conducted with the cationic cluster show that it induces apoptosis, although a biological target has not yet been identified. Further research to establish the molecular targets of these compounds and to develop improved organometallic clusters as potential breast cancer therapeutics is underway.