Cytotoxic Triosmium Carbonyl Clusters: A Structure–Activity Relationship Study

Abstract

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-n Ln , 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.

Synthesis of Nanoporous Carbon–Cobalt‐Oxide Hybrid Electrocatalysts by Thermal Conversion of Metal–Organic Frameworks

“…Promising candidates include a complex of osmium phenylazopyridine reported by Sadler, which exhibited potent cytotoxicity against A2780 ovarian cancer cells 22,23. We have also recently reported osmium carbonyl clusters that exhibited cytotoxicity against both MCF‐7 and MDA‐MB‐231 breast cancer cells 24–26. These results prompted us to synthesize the three osmium analogues of the ferrocifens (Scheme ).…”

Osmocenyl-tamoxifen derivatives target the thioredoxin system leading to a redox imbalance in Jurkat cells

“…To that can be added the variety of available metals [2] and, for the transition elements, the potential availability of several degrees of oxidation. 3 With organometallic complexes of gold [8,9], those from the group 8 triad, particularly of Fe and Ru, are amongst the most widely studied [10][11][12][13] with the notable exception to date of Os [14][15][16][17]. This heavy element offers a capacity for good stabilization of certain high degrees of oxidation (+VI) and for an excellent metal-to-ligand back-donation at low oxidation states (+II, +III) leading to more stable complexes than those of Fe or Ru in biological media.…”

The length of the bridging chain in ansa-metallocenes influences their antiproliferative activity against triple negative breast cancer cells (TNBC)

“…[20][21][22] However, it has not been possible to eradicate a number of serious secondary effects caused by these medications, in particular their high level of general toxicity and tendency to induce resistance. 20 Inspired by the success of platinum compounds, other transition metals have been intensively studied, most recently in organometallic form, for example with Fe, 12,13,16,[23][24][25][26] Ru, 3,[27][28][29][30] Au, 8 Os, 15,31 Ir, 32 rhodium, 33,34 and some of these have now reached the clinical trial stage. Fc-OH-TAM…”