Review on Therapeutic Applications of Hydrazine‐Based Ligands and Their Metal Complexes in Medicinal Chemistry

ABSTRACT Drugs are rapidly becoming ineffective against microbial infections, necessitating the development of new and more effective therapeutic strategies. Hydrazine‐based ligands have emerged as promising candidates in medicinal chemistry because of their structural flexibility, multiple donor centers, redox properties, and amenability to chemical modification. These characteristics enable diverse coordination modes with metal ions and facilitate the modulation of biological activity with mechanisms distinct from those of conventional drugs. Complexes incorporating metals exhibit significant antibacterial, antifungal, anticancer, antioxidant, and antitubercular activities and enhance the efficacy of uncoordinated ligands. The biological activities arise from synergistic effects, including reactive oxygen species (ROS) generation, enzyme inhibition, and interactions with DNA or proteins. Pro‐metallodrug strategies have the potential to enhance selectivity and minimize off‐target toxicities. Recent advancements have integrated experimental methodologies with computational approaches, including density functional theory (DFT), molecular docking, ADMET prediction, and nanotechnology‐based delivery systems to optimize therapeutic outcomes. However, current research is fragmented, and a more systematic understanding of the relationships between metal identity, coordination environment, redox behavior, and biological effects is needed. This review highlights recent progress in elucidating the structure–activity relationships (SARs) and practical synthetic methodologies, providing a framework for the rational design of safe, effective, and economically viable hydrazine‐based metallodrugs.