Cytotoxic triosmium carbonyl clusters : a structure-activity relationship study

• Main Authors: Top, Siden, Vessières, Anne, Leong, Weng Kee, Lee, Shirley Hui Zhi
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2014
• Subjects: DRNTU::Science::Biological sciences::Biochemistry
• Online Access: https://hdl.handle.net/10356/100836; http://hdl.handle.net/10220/19690
• Institution: Nanyang Technological University

A structure–activity relationship (SAR) study of the triosmium carbonyl cluster Os3(CO)10(NCCH3)2 was carried out with a series of clusters of the general formula Os3(CO)12−nLn, 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 IC50 value of 3 μM 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.