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.
Complexes [Au(2)(H(2)Gy3DH)(2)]Cl(2) (1), [Au(H(2)Gy3Me)]Cl(3) (2) and [Au(H(2)Gy3Et)]Cl(3) (3) were obtained with glyoxaldehyde bis(thiosemicarbazone) (H(2)Gy3DH) and its N(3)-methyl (H(2)Gy3Me) and N(3)-ethyl (H(2)Gy3Et) derivatives. The bis(thiosemicarbazones) and their gold(I) and gold(III) complexes exhibited anti-proliferative activity against HL-60, Jurkat (leukemia) and MCF-7 (breast cancer) cells at 10 μmol L(-1). Complex (2) was able to in vitro inhibit thioredoxin reductase (TrxR) activity, which suggests that inhibition of TrxR could be part of its mechanism of action.
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