Extrapolating the Fragment-Based Approach to Inorganic Drug Discovery

The fragment-based approach is a well-established strategy for organic drug discovery. Recent studies have shown that this approach also has considerable potential in medicinal inorganic chemistry, and yet the approach has not been formally described. Here, we describe selected compounds that form ( or have potential to form) intra- or inter-DNA-DNA, DNA-protein, and protein-protein crosslinks. Such dual interactions provide a powerful way to generate metal-based drugs with superior efficacies to those currently used. We demonstrate that the fragment-based approach represents an ideal way to design these bioactive compounds. In this review, we point out the limitations of current examples and delineate key components that might lead to more effective compounds (i.e., compounds that are more selective and have stronger binding affinities for specific biomolecular targets).