Inhibition of histone deacetylases, topoisomerases and epidermal growth factor receptor by metal-based anticancer agents: Design & synthetic strategies and their medicinal attributes.

Metal-based inhibitors of histone deacetylases (HDAC), DNA topoisomerases (Topos) and Epidermal Growth Factor Receptor (EGFR) have demonstrated their cytotoxic potential against various cancer types such as breast, lung, uterus, colon, etc. Additionally, these have proven their role in resolving the resistance issues, enhancing the affinity, lipophilicity, stability, and biocompatibility and therefore, emerged as potential candidates for molecularly targeted therapeutics. This review focusses on nature and role of metals and organic ligands in tuning the anticancer activity in multiple modes of inhibition considering HDACs, Topos or EGFR as one of the primary targets. The conceptual design and synthetic approaches of platinum and non-platinum metal complexes comprising of chiefly ruthenium, rhodium, palladium, copper, iron, nickel, cobalt, zinc metals coordinated with organic scaffolds, along with their biological activity profiles, structure-activity relationships (SARs), docking studies, possible modes of action, and their scope and limitations are discussed in detail.