Biological applications of thiocarbohydrazones and their metal complexes: A perspective review

Although organic compounds account for more than 99% of currently approved clinical drugs, the established clinical use of cisplatin in cancer or auranofin in rheumatoid arthritis have paved the way to several research initiatives to identify metal-based drugs for a wide range of human diseases. Nitrogen and sulfur donor ligands, characterized by different binding motifs, have been the subject in recent years of one of the main research areas in coordination chemistry. Among the nitrogen/sulfur compounds, very little is known about thiocarbohydrazones (TCH), the higher homologues of the well-known thiosemicarbazones (TSC), and their metal complexes. The extra hydrazine moiety provides the ligands of variable metal binding modes, structural diversity and promising biological implications. The interesting coordination chemistry of TCH has mainly been focused on symmetric derivatives, which are relatively simple to synthesize while few examples of asymmetric ligands have been reported. This informative review on TCHs and their metal complexes will be helpful for improving the design of metal-based pharmaceuticals for applications ranging from anticancer to antinfective therapy.