Metal complexes as inhibitors of transcription factor activity

Transcription factors are molecules that play a fundamental role in regulating the expression of the human genome. These proteins bind to cognate sequences within the regulatory regions of genes, thereby controlling the flow of genetic information from DNA to mRNA. Due to their vital role in maintaining biological processes such as cellular specialization and growth, aberration in transcription factor signalling can lead to the pathogenesis of a number of human disorders, including cancer and inflammatory diseases. While the development of organic small molecules as modulators of transcription factor activity has gained significant momentum over the past few years, the application of transition metal complexes for the same purpose has garnered comparatively less attention. In this review, we survey recent examples in the development of transition metal complexes as inhibitors of transcription factor activity. The mechanisms of transcription factor inhibition covered include direct binding of transcription factors, binding to DNA consensus sequences, and inhibition of upstream targets. The studies presented here demonstrate that the unique properties of metal complexes can be effectively harnessed to develop promising tools for studying or modulating transcription in biological systems. (C) 2013 Elsevier B.V. All rights reserved.