2-Benzoylpyridine-N(4)-tolyl thiosemicarbazones and their palladium(II) complexes: cytotoxicity against leukemia cells.

Abstract

The palladium(II) complexes [Pd(2Bz4oT)Cl], [Pd(2Bz4mT)Cl], and [Pd(2Bz4pT)Cl] were prepared with N(4)-ortho- (H2Bz4oT) N(4)-meta- (H2Bz4mT) and N(4)-para- (H2Bz4pT) tolyl-thiosemicarbazones derived from 2-benzoylpyridine. The free thiosemicarbazones proved to be highly cytotoxic against Jurkat, HL60 and the resistant HL60.Bcl-X(L) leukemia cell lines at nanomolar concentrations, but were much less cytotoxic to HepG2human hepatoma cells. Upon coordination to palladium(II) the cytotoxic activity against all studied cell lines decreases. However, the high cytotoxicity of the free thiosemicarbazones against leukemia, together with their hepatotoxic profile similar to that of cisplatin suggest that N(4)-tolyl thiosemicarbazones have potential as chemotherapeutic drug candidates.

• Authors: Karina S O Ferraz, Lucas Ferandes, Diego Carrilho, Mauro C X Pinto, Maria de Fátima Leite, Elaine M Souza-Fagundes, Nivaldo L Speziali, Isolda C Mendes, Heloisa Beraldo
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 17 Issue 20 Pg. 7138-44 (Oct 15 2009) ISSN: 1464-3391 [Electronic] England
• PMID: 19773176 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-benzoylpyridine N(4)-methylthiosemicarbazone
• Antineoplastic Agents
• Thiosemicarbazones
• Palladium

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Cell Line, Tumor
• Crystallography, X-Ray
• Drug Screening Assays, Antitumor
• Humans
• Leukemia (pathology)
• Magnetic Resonance Spectroscopy
• Models, Molecular
• Palladium (chemistry)
• Thiosemicarbazones (chemistry, pharmacology)