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

• Published in: Bioorganic & medicinal chemistry Vol. 17; no. 20; pp. 7138 - 7144
• Main Authors: Ferraz, Karina S.O., Ferandes, Lucas, Carrilho, Diego, Pinto, Mauro C.X., Leite, Maria de Fátima, Souza–Fagundes, Elaine M., Speziali, Nivaldo L., Mendes, Isolda C., Beraldo, Heloisa
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15-10-2009; Elsevier
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Line, Tumor; Crystallography, X-Ray; Drug Screening Assays, Antitumor; General aspects; Humans; Leukemia; Leukemia - pathology; Magnetic Resonance Spectroscopy; Medical sciences; Models, Molecular; Palladium - chemistry; Palladium(II) complexes; Pharmacology. Drug treatments; Thiosemicarbazones; Thiosemicarbazones - chemistry; Thiosemicarbazones - pharmacology; Thiosemicarbazones; Leukemia; Palladium(II) complexes; Antineoplastic agent; Divalent metal Complexes; Molecular structure; Toxicity; Liver; Cytotoxicity; Pyridine derivatives; Hepatocyte; T-Lymphocyte; Tumor cell; Human; Promyelocytic leukemia; Thiosemicarbazone; Palladium II Complexes; Organic ligand; Transition metal Complexes; X ray diffraction; In vitro; HL60 cell line; Position isomer; Cell line; Platinoid Complexes; Toluene derivatives; Crystalline structure
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2009.08.063

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 HepG2
human 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.