Hydrazide-hydrazone/hydrazone as enabling linkers in anti-cancer drug discovery: A comprehensive review

The burgeoning demand for novel cytotoxic drugs possessing improved bioavailability and safety profiles has spurred the hybridization of various pharmacophores in the past decades. Among the numerous available linkers for this purpose, hydrazide-hydrazone/hydrazone linkers have emerged as highly promising options due to their enhanced hydrolytic stability and straightforward synthesis. The utilization of these linkers has allowed chemists to synthesize novel hybrids and metal-complexes with enhanced target selectivity towards proteins like kinases, tubulin, topoisomerases, or carbonic anhydrases. This comprehensive review sheds light on the pivotal role played by hydrazide-hydrazone/hydrazone linkers in the development of therapeutic agents, especially those showcasing potent antiproliferative activity in the most recent years. Additionally, it provides a robust foundation for the identification and design of promising scaffolds with hydrazide-hydrazone/hydrazone linkers as anticancer agents.