α-N-Heterocyclic thiosemicarbazones, (N)-TSCs, are potent inhibitors of ribonucleotide reductase (RR). This enzyme plays a critical role in DNA synthesis and repair, and is a well-recognized target for cancer chemotherapeutic agents. In this review the structural features of (N)-TSCs, required for maximum antitumour activity have been explored. Special attention is given to the mechanisms of action and structure-activity relationships.

The complexes [M(HL)L]ClO₄(HL = methyl 2-pyridyl ketone thiosemicarbazone; M = Cu 1 or Co 2) have been prepared from the reaction of HL with the appropriate perchlorate salt; [Cu(HL)L]NCS 3 was also prepared by transmetallation of [Pb₂(HL)L(NCS)₂]NCS with an excess of copper(II) perchlorate. The new complexes have been characterized by spectroscopic techniques and the crystal structure of 3 has been determined: green triclinic crystal, a= 10.150(2), b= 10.350(2), c= 11.890(2)Å, α= 88.55(3), β= 83.28(3), γ= 63.26(3)°, space group P, Z= 2. The copper atom is six-co-ordinated by two NNS donor sets from terdentate ligands.

Thiosemicarbazones (TSCNs) constitute a broad family of compounds (R₁R₂C=N-NH-C(S)- NR₃R₄), particularly attractive because many of them display some biological activity against a wide range of microorganisms and cancer cells. Their activity can be related to their electronic and structural properties, which offer a rich set of donor atoms for metal coordination and a high electronic delocalization providing different binding modes for biomolecules. Heterocycles such as pyrrole, imidazole and triazole are present in biological molecules such as Vitamine B12 and amino acids and could potentially target multiple biological processes. Considering this, we have explored the chemistry and biological properties of thiosemicarbazones series and their complexes bearing heterocycles such as pyrrole, imidazole, thiazole and triazole. We focus at the chemistry and cytotoxicity of those derivatives to find out the structure activity relationships, and particularly we analyzed those examples with the TSCN units in which the mechanism of action information has been profoundly studied and pathways determined, to promote future studies for heterocycle derivatives.