Medicinal Chemistry Targeting Mitochondria: From New Vehicles and Pharmacophore Groups to Old Drugs with Mitochondrial Activity.

摘要: Interest in tumor cell mitochondria as a pharmacological target has been rekindled recent years. This attention is due part to new publications documenting heterogenous characteristics of solid tumors, including anoxic and hypoxic zones that foster cellular populations with differentiating metabolic characteristics. These include tumor-initiating or cancer stem cells, which have strong capacity adapt reduced oxygen availability, switching rapidly between glycolysis oxidative phosphorylation sources energy metabolites. Additionally, this subpopulation shows high chemo- radioresistance for repopulation. Interestingly, it shown inhibiting mitochondrial function cells affects pathways, bioenergy, viability. Therefore, inhibition may be viable strategy eradicating cells. In context, medicinal chemistry research over the last decade synthesized characterized "vehicles" capable transporting novel existing pharmacophores based on mechanisms exploit physicochemical properties vehicles inherent mitochondria. The pharmacophores, some isolated from plants others, were lab, are diverse chemical nature. Some these molecules active, while others prodrugs evaluated alone linked mitochondria-targeted agents. Finally, researchers recently described drugs well-proven safety efficacy exert mitochondria-specific inhibitory effect through noncanonical mechanisms. effectiveness improved by linking them carrier molecules. promising agents should combination classic chemotherapeutic clinical studies.