title: Platinum(II) and palladium(II) complexes with 2-acetyl pyridine 4N-ethyl thiosemicarbazone able to overcome the cis-platin resistance. Structure, antibacterial activity and DNA strand breakage.
abstract: The reactions of Pd(II) and Pt(II) with 2-Acetyl Pyridine N(4)-Ethyl-Thiosemicarbazones, HAc4Et and 2-Acetyl Pyridine N(4)-1-(2-pyridyl)-piperazinyl Thiosemicarbazone, HAc4PiPiz and 2-Formyl Pyridine N(4)-1-(2-pyridyl)-piperazinyl Thiosemicarbazone, HFo4PiPiz afforded the complexes, [Pd(Ac4Et)], 1, [Pd(HAc4Et)2]Cl2, 2 and [Pd(Ac4Et)2], 3 [Pt(Ac4Et)], 4, [Pt(HAc4Et)2]Cl2, 5, [Pt(Ac4Et)2], 6 and [Pd(Fo4PipePiz)Cl], 7, [Pd(Fo4PipePiz)2], 8, [Pd(Ac4PipePiz)Cl], 9 and [Pd(Ac4PipePiz)2], 10. The crystal structure of the complex [Pt(Ac4Et)2], 6 has been solved. The platinum(II) atom is in a square planar environment surrounded by two cis nitrogen atoms and two cis sulfur atoms. The ligands are not equivalent, one being tridentate with (N,N,S) donation, the other being monodentate using only the sulfur atom to coordinate to the metal. The tridentate ligand shows a Z, E, Z configuration while the monodentate ligand shows an E, E, Z. Inter-molecular hydrogen bonds stabilize the structure, while the crystal packing is determined by pi-pi, and Pt-C interactions. The antibacterial effect of Pd(II) and Pt(II) complexes were studied in vitro. The complexes were found to have effect on Gram(+) bacteria, while the same complexes showed no bactericidal effect on Gram(-) bacteria. The effect of the Pd(II) and Pt(II) complexes on the in vitro DNA strand breakage was studied by agarose gel electrophoresis. The complexes 1-6 were found to exhibit a cytotoxic potency in a very low micromolar range and to be able to overcome the cisplatin resistance of A2780/Cp8 cells.
authors.affiliation: Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece. dkovala@cc.uoi.gr
authors.forename: Dimitra
authors.initials: D
authors.lastname: Kovala-Demertzi
authors.forename: Mavroudis A
authors.initials: MA
authors.lastname: Demertzis
authors.forename: Eleni
authors.initials: E
authors.lastname: Filiou
authors.forename: Anastasia A
authors.initials: AA
authors.lastname: Pantazaki
authors.forename: Paras N
authors.initials: PN
authors.lastname: Yadav
authors.forename: John R
authors.initials: JR
authors.lastname: Miller
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Dimitrios A
authors.initials: DA
authors.lastname: Kyriakidis
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004249:DNA Damage; D024881:Drug Resistance, Bacterial; D004587:Electrophoresis, Agar Gel; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000235:genetics; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000235:genetics; D006860:Hydrogen Bonding; D008024:Ligands; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010165:Palladium / Q000737:chemistry; D010984:Platinum / Q000737:chemistry; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D008024:Ligands; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; D010984:Platinum; D010165:Palladium; D002945:Cisplatin