α(N)-Heterocyclic Thiosemicarbazones: Iron Chelators that are Promising for Revival of Gallium in Cancer Chemotherapy

Author(s): Shuhong Cao, Xiahui Chen, Ligen Chen, Jingwen Chen.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 16 , Issue 8 , 2016

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Abstract:

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.

Keywords: Gallium, anticancer activity, sulfur-containing chelator, thiosemicarbazone, structure-activity relationships, complexation effect.

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Article Details

VOLUME: 16
ISSUE: 8
Year: 2016
Page: [973 - 991]
Pages: 19
DOI: 10.2174/1871520616666160310142012
Price: $58

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