di-2-pyridylketone-4-4-dimethyl-3-thiosemicarbazone and Neoplasms

Currently, cancer and its progression to metastasis result in a large number of deaths. The lack of new drugs, appropriate clinical trials for metastasis preventive drugs and incomplete understanding of the molecular machinery are the major obstacles in metastasis prevention and treatment. On the other hand, thiosemicarbazones and their bioisosteres, thiazole and thiazolidinone are recurring in a wide range of biologically active compounds that reach different targets within tumor context and represent a promising start point to access potential candidates in metastatic cancer. Therefore, the search for new lead compounds showing highest anticancer potency and less adverse effects is the major challenger in drug discovery. The search was based from 1994 to 2018, focusing on thiosemicarbazone, thiazole and thiazolidinone cores that allowed us to discuss how the three multi-target motifs have been used for the target-based design and development of anticancer agents. In the lasts years, thiosemicarbazone, thiazole, and thiazolidinone cores are recurrent in many approaches for cancer therapy. In our search, it was verified that due to its biodiversity and versatility the anticancer potential of such structures has been assigned to distinct mechanisms reinforcing the value of these cores in the anticancer drug development. The present article aims point out the current application of thiosemicarbazone, thiazole and thiazolidinone cores in the design of anticancer agents within tumor progression, acting via varied targets such as cathepsins, NDRG1 gene and kinases, showing in vitro tests, in vivo tests and clinical trials. In our search it was possible to verify that thiazole is the most studied and the most important of the three structures. Therefore, we hope to provide new insights and valuable inspiration in the research of new drugs and development and contribute to the management of cancer.

Topics: Animals; Antineoplastic Agents; Cell Cycle Proteins; Disease Progression; Drug Delivery Systems; Drug Discovery; Humans; Intracellular Signaling Peptides and Proteins; Neoplasms; Thiazoles; Thiazolidines; Thiosemicarbazones

Iron chelators have emerged as a potential anti-cancer treatment strategy. In this study, a series of novel thiosemicarbazone iron chelators containing a quinoline scaffold were synthesized and characterized. A number of analogs show markedly greater anti-cancer activity than the 'gold-standard' iron chelator, desferrioxamine. The anti-proliferative activity and iron chelation efficacy of several of these ligands (especially compound 1b), indicates that further investigation of this class of thiosemicarbazones is worthwhile.

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Deferoxamine; Humans; Iron; Iron Chelating Agents; Neoplasms; Quinolines; Thiosemicarbazones