An Investigation into Ruthenium-based Carbene- and Sandwich Complexes as Potential Histone Deacetylase Inhibitors

Abstract

A novel, ruthenium(II)-based, p-cymene-capped sandwich complex with a hydroxamic acid functionality, designed as an organometallic variation of known effective HDAC inhibitors, was synthesised. Additionally, the pharmacological activity of this complex was assessed in both an MTT assay with the H460 non-small cell lung carcinoma cell line and a fluorometric HDAC assay, which yielded IC50 values of 7.4 ± 4.8 μM and between 0.1 and 1 μM respectively. These results provide the groundwork for extensive exploration into the optimisation and development of a novel class of anticancer agents. The synthesis of the benzene-capped analogue of this complex was attempted, but not achieved. However, insights are provided into why the synthesis was unsuccessful, thereby providing a basis for its synthesis in future work.

Furthermore, several synthetic routes towards a novel, N-heterocyclic carbene-containing ruthenium(II) piano stool complex - also a candidate HDAC inhibiting anticancer agent - were attempted. Though the complex was not successfully isolated through any of the explored routes, a thorough investigation into carbene chemistry in both organometallic and purely organic contexts has been undertaken. This work not only contributes to a general understanding of an emerging branch of synthetic chemistry, but also establishes a basis from which the synthesis of such candidates can be more readily realised.