Taste Responses to the Optical Isomers of Potassium Warfarin and Dipotassium Glutamyl Glutamate and the Synergistic Response to a Mixture of Both Substances in Mice

Four- and five-coordinate platinum(II) complexes, cis-[PtCl2(A2)] (1) and [PtCl2(A2)(eta2-ethylene)] (2) {A2 = 4,7-diphenyl-1,10-phenanthroline disulfonic acid disodium salt, BPS (mixture of isomers) (a); 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline disulfonic acid disodium salt, BCS (mixture of isomers) (b)} have been synthesized and characterized by 1H, 13C, and 195Pt NMR spectroscopy. The stability and high water solubility of complexes 1a, 1b and 2b, due to the presence of the polar SO3- groups on the ligands skeleton, allowed to test their in vitro cytotoxicity on HeLa tumour cells in a wide range of drug concentration. At low and medium incubation doses (<200 microM) 1a, 1b and 2b all showed similar in vitro cytotoxicity, negligible or much lower with respect to cisplatin. At doses higher than 200 microM their activity increased and 1b, the most active among the new complexes, exhibited a cytotoxicity comparable, although still lower, with respect to cisplatin. GFAAS Platinum analytical data showed that the tested compounds 1a, 1b and 2b, although carrying sulfonate charged groups, may undergo cellular uptake, which, in the case of 1b and 2b, is even higher with respect to cisplatin. Furthermore, in the case of 1b and 2b it has been possible to compare, for the first time, the cytotoxic activity for square-planar four-coordinate and trigonal-bipyramidal five-coordinate platinum(II) complexes having the same carrier ligand. The tendency of the five-coordinate species 2b to give at longer incubation time similar cytotoxicity with respect to the square-planar compound 1b suggests a possible use of the trigonal-bipyramidal five-coordinate complexes as prodrugs.

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New water-soluble platinum(ii) phenanthroline complexes tested as cisplatin analogues: first-time comparison of cytotoxic activity between analogous four- and five-coordinate species

Pascali

Migoni

Papadia

et al. 2006

Dalton Trans.

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Taste Responses to the Optical Isomers of Potassium Warfarin and Dipotassium Glutamyl Glutamate and the Synergistic Response to a Mixture of Both Substances in Mice

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New water-soluble platinum(ii) phenanthroline complexes tested as cisplatin analogues: first-time comparison of cytotoxic activity between analogous four- and five-coordinate species

New water-soluble platinum(ii) phenanthroline complexes tested as cisplatin analogues: first-time comparison of cytotoxic activity between analogous four- and five-coordinate species

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