ABSTRACT
Four novel Pd2+ and Pt2+ mononuclear π-coordination compounds with general formula [M(HL)1,2Cl2], M=Pd2+, Pt2+ have been synthesized by reaction of [PdCl4]2-, [PtCl4]2- anions with N-allyl-4-morpholinethiocarboxamide (HL1) and N-Allyl-N'-tert-butylthiourea (HL2). All complexes have been characterized by single-crystal X-ray diffraction study and 1H, 13C NMR spectroscopy. Cytotoxic, cytostatic and proapoptotic activities of compounds have been determined in vitro on HeLa cell line and compared with cisplatin as etalon drug. All complex compounds possessed pronounced cytotoxic activity with IC50 indexes in range of 2·10-6-1.5·10-4Ð (IC50 of cisplatin is 5.7â10-5Ð) and showed proapoptotic, cytostatic and antisyntetic influence higher or comparable with cisplatin. The comparative influence of cisplatin and synthesized metal complexes on pTZ19R* plasmid DNA was monitored by agarose gel electrophoresis. All compounds showed high affinity to DNA that correlates with observed cytostatic and proapoptotic levels. In general Pd(II) compounds showed higher activity than Pt(II) ones.
Subject(s)
Coordination Complexes/chemical synthesis , Coordination Complexes/pharmacology , DNA/chemistry , Palladium/chemistry , Platinum/chemistry , Thiourea/analogs & derivatives , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Coordination Complexes/chemistry , HeLa Cells , Humans , Inhibitory Concentration 50 , Thiourea/chemistry , X-Ray DiffractionABSTRACT
Pd(I) and Ni(II) complex compounds: [Pd(AMMT)2]Cl2 (1), [Pd(AMMT)4]Cl2 (2) and [Ni(AMMT)2(H2O)](NO3)2 (3) with 4-amino-3-mercapto-5-methyl-1,2,4-triazole (AMMT) have been synthesized. The spectral characteristics of 1, 2 were studied by 1H (13C) NMR and UV-Vis spectroscopy. X-ray diffraction studies established that all complexes contain the AMMT molecule, which are coordinated to the central metal ion in the thione tautomeric form. At the ratio M: L = 1:2 ligand is coordinated in bidentate chelate manner by the nitrogen of amino- and sulfur of mercapto group (compounds 1, 3). But the molar ratio M: L = 1:4 leads to monodentate coordination of AMMT molecules only by sulfur of mercaptogroup (complex 2). Vacant coordination sites of the metal ion are occupied by water molecules (complex 3). The screening of complexes 1-3 and starting compounds [AMMT, K2PdCl4 (4), Ni(NO3)2 · 6H2O (5)] by their mitochondrial dehydrogenase activity have been performed by us for the first time, resulting in established that the Pd(II) complexes (1, 2), Pd(II) salt (4) and AMMT normalize the activity of mitochondrial dehydrogenases of cancer HeLa cells, identified by MTT-test. In contrast, the Ni(II) complex (3) and Ni(II) salt (5) do not stimulate the activity of mitochondrial dehydrogenases. It has been found, that all investigated compounds do not affect on the cell cycle and the level of apoptotic cells as well as do not show a toxic effect. Thus, these results indicate that AMMT and Pd(II) complexes may be used as modifiers of mitochondrial respiration, which dysfunction is particularly evident in the tumor cells.
Subject(s)
Coordination Complexes/pharmacology , Mitochondria/drug effects , Nickel/chemistry , Oxidoreductases/metabolism , Palladium/chemistry , Triazoles/chemistry , Cations, Divalent , Cell Cycle/drug effects , Cell Respiration/drug effects , Cell Survival/drug effects , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , HeLa Cells , Humans , Mitochondria/enzymology , Mitochondrial Proteins/agonists , Mitochondrial Proteins/metabolismABSTRACT
The title compound, NH(4) (+)·C(2)H(8)NO(6)P(2) (-)·2H(2)O, was obtained by the reaction between 1-amino-ethane-1,1-diyldiphospho-nic acid and ammonium hydroxide (1:1) in an aqueous solution. The asymmetric unit contains one anion with two H atoms transferred from the phospho-nic acid groups to the amino group of the anion and to an ammonia mol-ecule, giving an ammonium cation. The structure displays N-Hâ¯O and O-Hâ¯O hydrogen bonding, which creates a three-dimensional network.
ABSTRACT
The title compound, H(3)O(+)·C(4)H(10)NO(6)P(2) (-)·H(2)O, was obtained from the reaction of cyclo-propane-carbonitrile with PCl(3), followed by dropwise addition of water. The asymmetric unit comprises an oxonium cation, a zwitterionic monoanion containing a positively charged ammonium group and two negatively charged phospho-nic acid residues and a water mol-ecule of crystallization. The hydroxonium cation and water mol-ecule are hydrogen bonded to the anion and further N-Hâ¯O and O-Hâ¯O bonds create a three-dimensional network.
ABSTRACT
The title compound, C(5)H(15)NO(6)P(2), was obtained by the reaction of penta-nenitrile with PCl(3) followed by the dropwise addition of water. The asymmetric unit contains one mol-ecule, which exists as a zwitterion with a positive charge on the -NH(3) group and a negative charge on one of the phospho-nic O atoms. The crystal structure displays N-Hâ¯O and O-Hâ¯O hydrogen bonding, which creates a three-dimensional network.
