Topics in Anti-Cancer Research

Volume: 3

Indexed in: Book Citation Index, Science Edition (BKCI-S), Chemical Abstracts, BIOSIS Previews, EBSCO, Ulrich's Periodicals Directory.

This is the third volume of the Patent eBook Series entitled Topics in Anti-Cancer Research. This eBook comprises updated reviews on topics relevant to modern cancer research published in the journal ...
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Aryl- and Heteroaryl-Thiosemicarbazone Derivatives and Their Metal Complexes: A Template for Pharmacological Activities

Pp. 446-483 (38)

Narayana S.H.N. Moorthy, Nuno M.F.S.A. Cerqueira, Maria J. Ramos and Pedro A. Fernandes


In this chapter, we discuss the current patents concerning aryl/heteroaryl thiosemicarbazone derivatives as regard to their activities and properties, including coordination (chelation) properties. The mode of action of the aryl/heteroaryl thiosemicarbazone derivatives involves metal coordination with proteins or biological fluids that have metal ions in their structure. Additionally, these molecules can also form multiple hydrogen bonds through their (thio) amide and N3 nitrogen that ensure a strong interaction with the receptor. In some cases, strong π-π interactions can be observed between the aryl/heteroaryl rings and the tyrosine or other aromatic amino acids. Special attention is given to pyridyl, bis-pyridyl, benzoylpyridyl and isatin thiosemicarbazone derivatives that exhibit significant anticancer, antiviral and other activities in free and in metal complex forms. This key biological role is often related with their capability to inhibit the enzyme ribonucleotide reductase, similar to what is observed with potent anticancer drugs such as Triapine ((3-aminopyridine-2- carboxaldehyde thiosemicarbazone) (3-AP)) and methisazone. Recent studies have revealed that thiosemicarbazone can also inhibit topoisomerase IIα enzyme. Thiosemicarbazone derivatives form coordination complex with various metals such as Zn, Cu, Fe, Co, Ni, Pt, Pd, etc, and these complexes provide better activities than the free thiosemicarbazones. Recent patents show that the controlled or sustained release dosage form of the thiosemicarbazone derivatives along with ionizing radiations is used for the treatment of proliferative diseases (US20110152281, US20110245304, US20120172217, WO2012079128 and WO2013082661).


Benzoylpyridyl, bis-pyridyl, cancer, chelation, copper(II), cytotoxicity, DNA, hydrogen bonding, iron (II), isatin, MDR, metal complexes, Pglycoprotein, proliferative diseases, pyridyl, redox, ribonucleotide reductase, semicarbazone, thiosemicarbazones, topoisomerase, zinc (II).


REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, s/n, Rua do Campo Alegre, 4169-007 Porto, Portugal.