The metal-based drugs have gained increasing attention in the fight against cancer.
Ga(III) in the form of inorganic salts has demonstrated efficacy in the treatment of a number of
malignancies in experimental animals and humans, and has therefore attracted considerable
pharmaceutical interest. However, the poor hydrolytic stability of Ga(III) in physiological
medium owing to its property of hard Lewis acid prevents its widespread use in systemic cancer
chemotherapy. Complexation of suitable chelators capable of stabilising Ga(III) against
hydrolysis affords an opportunity for overcoming this drawback. Thiosemicarbazone (TSC)
derivatives, a class of well-studied iron chelators featuring softer donor sulfur, also were
evaluated to possess antineoplastic activities in an arrary of tumour cell lines. The structural
modifications can affect the activities of TSCs, and related structure-activity relationships
(SAR) have been studied over these years. Combination of Ga(III) and TSCs that are both
pharmaceutically active has proved to exert synergistic effects of each component in one
compound in most cases, and may produce more potent Ga(III) drugs. In this review, the SAR
of α(N)-heterocyclic thiosemicarbazone (HCT) analogues, a family of TSCs, were scrupulously surveyed, and the
effect of Ga(III) complexation on their anticancer activity sparsely reported in literature was comparatively examined,
in order to stimulate further advances in the field of gallium-based anticancer drugs.