Comparative biological applications of Zn(II) and Cd(II) thiosemicarbazone complexes

Thiosemicarbazone ligands and their transition-metal complexes have attracted considerable attention in medicinal inorganic chemistry due to their versatile coordination modes and broad pharmacological potential. This review presents recent studies (2020-2025) on the comparative evaluation of the biological applications of Zn(II) and Cd(II) thiosemicarbazone complexes incorporating N,S-, N,N,S-, and N,S,O-donor ligand systems. The compiled studies demonstrate that metal coordination considerably enhances antimicrobial, anticancer, antioxidant, and anti-inflammatory activities compared to free ligands, primarily due to chelation-induced lipophilicity, improved cellular uptake, and stronger biomolecular interactions. Comparative structure-activity relationship analysis indicates that biological activity is strongly influenced by metal ion identity, ligand denticity, donor atom set, and coordination geometry. In particular, tridentate N,N,S- and N,S,O-donor systems generally exhibit superior biological activity compared to bidentate N,S analogues. Furthermore, differences in biological responses between Zn(II) and Cd(II) complexes highlight the important role of metal-ion characteristics in determining pharmacological behaviour. In general, Zn(II) and Cd(II) thiosemicarbazone complexes emerge as promising candidates for multifunctional biological applications and provide valuable insights for the rational design of next-generation metal-based therapeutic agents. However, studies on the antioxidant and anti-inflammatory activities of these complexes remain comparatively limited relative to antimicrobial and anticancer investigations, highlighting the need for further systematic exploration of these biological properties.