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.