Structural Modifications for Biological Activity Enhancements in Thiosemicarbazone Scaffolds and their Metal Complexes

The molecular weight of a typical small-molecule drug is usually less than 500 Da. Small molecules can influence the function of different proteins by interacting with their targets and forming complexes. Thiosemicarbazones (TSCs) are biologically important Schiff base ligands. Due to their considerable biological importance, they have been explored for an extended period. TSC complexes exhibit structural diversity, varied bonding patterns, and hold promise for their biological importance, as well as ion-sensing properties. This review explores the medicinal applications of TSC complexes and the effect of different factors like molecular weight, structural alterations, presence of benzene ring and electron-donating and withdrawing groups in the TSC moiety. Molecules in compliance with Lipinski’s rule had enhanced activity. Complexes with low molecular weight also possessed better Absorption, distribution, metabolism and excretion (ADME) characteristics, and good to moderate bioactivity scores. Mixed-ligand complexes have also been discussed, showing that synergetic effect may enhance the overall stability of the complex. Small molecules can be utilized as medicinal agents and as chemical probes for the exploration of new drug targets and through structural biology, crucial interactions between the molecules and drug targets can be comprehended, thereby propelling target-based drug discovery.