Structure-Activity Modelling of Mitochondrial Dysfunction

Abstract

The link that has been established between mitochondrial dysfunction and organ-level toxicity is an important breakthrough for the assessment of human health risks in drug discovery, the cosmetics industry, and other chemical sectors. The ability to identify potential problematic chemicals as early as possible in the development phase is a key requirement for these industries. This chapter outlines in silico methods that enable a mechanistic link between mitochondrial toxicity and chemistry to be established. There is a clear need to develop structural alerts (and/or structure-activity models) to other mechanisms capable of causing mitochondrial toxicity. The chapter outlines some of these structural alerts. It focuses on detailing the mechanistic chemistry associated with these structural alerts. This focus is due to the importance of mechanism-derived structural alerts toward the prediction of toxicology in drug discovery, the cosmetics sector, and the wider chemicals industry.