Antimony(III) complexes with 2-benzoylpyridine-derived thiosemicarbazones: cytotoxicity against human leukemia cell lines.
The antimony(III) complexes [Sb(2Bz4DH)Cl(2)] (1), [Sb(H2Bz4M)Cl(3)] x 2 H(2)O (2) and [Sb(2Bz4Ph)Cl(2)] (3) were obtained with 2-benzoylpyridine thiosemicarbazone (H2Bz4DH) and its N(4)-methyl (H2Bz4M) and N(4)-phenyl (H2Bz4Ph) derivatives. H2Bz4DH, H2Bz4Ph and complexes (1-3) exhibited high cytotoxic activity against HL-60 and Jurkat human leukemia cell lines. When these compounds were tested against HL-60 cells with ectopic expression of BcrAbl, Bcl-2 or Bcl-X(L), which confer resistance to apoptosis against a variety of death-inducing agents, the cytotoxicity was much lower, indicating apoptosis to be part of their mechanism of action. The cytotoxic activity of complexes 2 and 3 against HL-60 and Jurkat cells was significantly higher than that of the corresponding thiosemicarbazones, suggesting coordination to be an interesting strategy of cytotoxic dose reduction.
Reis
Débora C
DC
Departamento de Química, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
Pinto
Mauro C X
MC
Souza-Fagundes
Elaine M
EM
Wardell
Solange M S V
SM
Wardell
James L
JL
Beraldo
Heloisa
H
D000965:Antimony / Q000737:chemistry*; D045744:Cell Line, Tumor; D055808:Drug Discovery; D006801:Humans; D020128:Inhibitory Concentration 50; D007938:Leukemia / Q000473:pathology*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013057:Spectrum Analysis; D013882:Thiosemicarbazones / Q000737:chemistry*; D014961:X-Ray Diffraction
D009942:Organometallic Compounds; D013882:Thiosemicarbazones; D000965:Antimony