Insights into molecular mechanisms of metallodrugs using metallomic studies
Sara La Manna, Daniela Marasco
Abstract
Metal ions are the center of an important class of therapeutics, i.e. metallodrugs for their unique coordination geometries and redox states. Many cellular functions depend on the interaction of metal ions with proteins, as well as the transport and uptake of metals into cells, storage and secretion which are regulated by peculiar control systems. The cellular redox homeostasis is regulated by a plethora of factors including metal ions that can produce reactive radicals and its dysregulation can lead to oxidative stress as observed in pathological conditions in many diseases as cancer, cardiovascular disease, diabetes, atherosclerosis, neurological disorders (Alzheimer’s, Parkinson’s disease) and chronic inflammation. Omics approaches can provide in-depth insights into the mechanisms of action (MOAs) of metallo-therapeutic compounds and metallomics is a proteomic tool that allows to investigate MOAs of metallodrugs, including their physiological metabolism (e.g., cellular distribution and biotransformation) and their molecular targets. Herein, we review the most recent and significant metallomic studies concerning metallodrugs in pathological cellular conditions including oxidative stress.