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

被引：51

作者：

Ferraz, Karina S. O. ^{[1
]}

Ferandes, Lucas ^{[2
]}

Carrilho, Diego ^{[2
]}

Pinto, Mauro C. X. ^{[2
]}

Leite, Maria de Fatima ^{[2
]}

Souza-Fagundes, Elaine M. ^{[2
]}

Speziali, Nivaldo L. ^{[3
]}

Mendes, Isolda C. ^{[1
]}

Beraldo, Heloisa ^{[1
]}

机构：

[1] Univ Fed Minas Gerais, Dept Quim, BR-31270901 Belo Horizonte, MG, Brazil

[2] Univ Fed Minas Gerais, Dept Fisiol & Biofis, BR-31270901 Belo Horizonte, MG, Brazil

[3] Univ Fed Minas Gerais, Dept Fis, BR-31270901 Belo Horizonte, MG, Brazil

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 20期

关键词：

Thiosemicarbazones; Palladium(II) complexes; Leukemia; BCL-X-L; RIBONUCLEOTIDE REDUCTASE; TOXICITY; INHIBITOR; ASSAY;

D O I：

10.1016/j.bmc.2009.08.063

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：7138 / 7144

页数：7

共 24 条

[1]

[Anonymous], EUR J MED CHEM

[2] The wide pharmacological versatility of semicarbazones, thiosemicarbazones and their metal complexes [J].

Beraldo, H ;

Gambino, D .

MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2004, 4 (01) :31-39

[3]

Bernstein LR, 1998, PHARMACOL REV, V50, P665

[4]

Boehl Markus, 2006, Journal of Pharmacological and Toxicological Methods, V54, P62, DOI 10.1016/j.vascn.2005.12.001

[5] Comparison of the anti-apoptotic effects of Bcr-Abl, Bcl-2 and Bcl-XL following diverse apoptogenic stimuli [J].

Brumatti, G ;

Weinlich, R ;

Chehab, CF ;

Yon, M ;

Amarante-Mendes, GP .

FEBS LETTERS, 2003, 541 (1-3) :57-63

[6] Increasing the antibacterial activity of gallium(III) against Pseudomonas aeruginosa upon coordination to pyridine-derived thiosemicarbazones [J].

da Silva, Jeferson G. ;

Azzolini, Lucas S. ;

Wardell, Solange M. S. V. ;

Wardell, James L. ;

Beraldo, Heloisa .

POLYHEDRON, 2009, 28 (11) :2301-2305

[7] Hierarchical cluster analysis of environmental pollutants through P450 induction in cultured hepatic cells - Indications for a toxicity screening test [J].

Dubois, M ;

Plaisance, H ;

Thome, JP ;

Kremers, P .

ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY, 1996, 34 (03) :205-215

[8] Utility and synthetic uses of Mannich reaction: An efficient route for synthesis of thiadiazino-[1,3,5][3,2-a]benzimidazoles [J].

El-Wareth, A ;

Sarhan, AO ;

Abdel-Hafez, SH ;

El-Sherief, H ;

Aboel-Fadl, T .

SYNTHETIC COMMUNICATIONS, 2006, 36 (08) :987-996

[9] Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone; 3-AP), an inhibitor of ribonucleotide reductase with antineoplastic activity [J].

Finch, RA ;

Liu, MC ;

Cory, AH ;

Cory, JG ;

Sartorelli, AC .

ADVANCES IN ENZYME REGULATION, VOL 39, 1999, 39 :3-12

[10] Triapine (3-aminopyridine-2-carboxaldehydethiosemicarbazone): A potent inhibitor of ribonucleotide reductase activity with broad spectrum antitumor activity [J].

Finch, RA ;

Liu, MC ;

Grill, SP ;

Rose, WC ;

Loomis, R ;

Vasquez, KM ;

Cheng, YC ;

Sartorelli, AC .

BIOCHEMICAL PHARMACOLOGY, 2000, 59 (08) :983-991

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