Amparo Alvarez-Valdés

Reactivity and biological properties of a series of cytotoxic PtI2(amine)2 complexes, either cis or trans configured.

Six diiodido-diamine platinum(II) complexes, either cis or trans configured, were prepared, differing only in the nature of the amine ligand (isopropylamine, dimethylamine, or methylamine), and their antiproliferative properties were evaluated against a panel of human tumor cell lines. Both series of complexes manifested pronounced cytotoxic effects, with the trans isomers being, generally, more effective than their cis counterparts. Cell cycle analysis revealed different modes of action for these new Pt(II) complexes with respect to cisplatin. The reactivity of these platinum compounds with a number of biomolecules, including cytochrome c, two sulfur containing modified amino acids, 9-ethylguanine, and a single strand oligonucleotide, was analyzed in depth by mass spectrometry and NMR spectroscopy. Interestingly, significant differences in the reactivity of the investigated compounds toward the various model biomolecules were observed: in particular we observed that trans complexes preferentially release their iodide ligands upon biomolecule binding, while the cis isomers may release the amine ligands with retention of iodides. Such differences in reactivity may have important mechanistic implications and a relevant impact on the respective pharmacological profiles.

Novel N-sulfonamide trans-platinum complexes: synthesis, reactivity and in vitro evaluation

In this work, we described for the first time the synthesis of trans-N-sulfonamide platinum complexes. The antiproliferative activity (GI50, μM) of these new compounds in human solid tumors cells was compared to cisplatin.

Synthesis and characterization of new cis-[PtCl2(isopropylamine)(amine′)] compounds: cytotoxic activity and reactions with 5′-GMP compared with their trans-platinum isomers

Abstract The synthesis and characterization of four new cis -platinum compounds of structural formula cis -[PtCl 2 (NH 2 CH(CH 3 ) 2 )(amine′)] (amine′=methylamine, dimethylamine, propylamine and butylamine) ( 2a – 2d ) are described. Cytotoxicity tests in tumor cell lines sensitive to cisplatin (CH1 and Pam 212) and resistant to cisplatin (CH1cisR, and Pam 212- ras ) indicate that only compound 2a possesses cytotoxic activity in the cisplatin-sensitive cell line CH1, albeit much less than cis -DDP and also less than corresponding trans -platinum compounds with mixed aliphatic amines. The interactions of cis - ( 2a – 2d ) and trans - ( 3a – 3d ) [PtCl 2 (NH 2 CH(CH 3 ) 2 )(amine′)] compounds with 5′-GMP in dilute NaClO 4 (10 mM) were investigated by 1 H NMR spectroscopy, and the progress of the reactions was followed overnight. In all cases two product peaks are observed in the cis -complexes, because the compounds are not symmetric. Temperature-dependent studies have been performed, but no significant variation in product structure is observed.

Expanding the synthesis of new trans-sulfonamide platinum complexes: cytotoxicity, SAR, fluorescent cell assays and stability studies.

In this manuscript, we describe the synthesis of new trans-N-sulfonamide platinum complexes and their antiproliferative activity (GI50, μM) in human solid tumors cells. The structure activity relationships (SAR), with different new synthesized complexes by variation in ligand, halogen and also in the stereochemistry of the ligand, has been studied. Solubility and stability studies have also been carried out as well as fluorescent cell assays in order to clarify the final target in the tumor cells.

Oxidation of anticancer Pt(II) complexes with monodentate phosphane ligands: towards stable but active Pt(IV) prodrugs

The synthesis, characterization and cytotoxicity studies of two novel platinum(IV) complexes, trans-PtCl4(dma)(PPh3), 1, and trans-PtCl4(ipa)(PPh3), 2, where dma is dimethylamine and ipa is isopropylamine, have been carried out. Both complexes contain aliphatic amines trans to phosphane ligands as a good alternative to take advantage of the phosphane group lipophilicity and the stability of platinum(IV) to obtain more effective drugs. Moreover, the complexes are stable in solution and such stability allowed their antitumoral action and DNA interaction to be checked and proved.

Reaction of folded acetate-bridged ortho-palladated complexes with CH2Cl2. Crystal structure of[{Pd(C6H5 CH2 N C (COC6H5) C6H4)(μ-Cl)}2]

Abstract Folded acetate-bridged ortho -palladated complexes of benzoylbenzylideneamines react with CH 2 Cl 2 to afford unfolded chlorobridged ortho -palladated complexes. This finding is supported by an X-ray crystallographic study of the complex [{Pd(C 6 H 5 CH 2  NC(COC 6 H 5 )C 6 H 4 )(μ-Cl)} 2 ].

Synthesis and characterization of complexes of PdII with 2-aminopyridine

SummaryThe synthesis and identification of the compoundstrans-bis(2-aminopyridine)dichloropalladium(II) and tetrakis(2-aminopyridine)palladium(II) chloride are described. The infrared spectra are discussed, particularly the metal-halogen and metal-ligand vibrations. Thermal decomposition was studied by differential thermal analysis (DTA) and thermogravimetry (TG).

Reactions of palladium (II) chloride with 1,4 - diphenyl - 2,3 - dimethyl - 1,4 - diazabutadiene and 1,4-DI(p-methoxyphenyl)-2,3-dimethyl- 1,4 - diazabutadiene

Abstract The reactions of palladium(II) chloride with 1,4 - diphenyl - 2,3 - dimethyl - 1,4 - diazabutadiene and 1,4 - di(p - methoxyphenyl) - 2,3 - dimethyl - 1,4 - diazabutadiene are described. With 1,4 - diphenyl - 2,3 - dimethyl - 1,4 - diazabutadiene diimine fission is produced, giving rise to a product identified by elemental analysis, IR and Raman spectra, and X-ray diffraction, as trans-dichlorobis(aniline) palladium(II). The complex is soluble in dimethylformamide and crystallizes with two molecules of solvent. The substance crystallizes in the monoclinic space group P21/n. The X-ray data were refined to R = 0.047 and Rw = 0.046. Final distances are Pd N = 2.060(5)Aand Pd C1 = 2.299(2)A. There are two bifurcated intermolecular N H ... C1 and C H... C1 hydrogen bonds which, together with one more intermolecular hydrogen bond N H... O, are responsible for the packing of the molecules. However, when 1,4 - di(p - methoxyphenyl) - 2,3 - dimethyl - 1,4 - diazabutadiene was treated with palladium chloride under the same conditions cis - dichloro - 1,4 - di(p - methoxyphenyl) - 2,3 - dimethyl - 1,4 - diazabutadiene was formed, as deduced from elemental analysis, and IR and Raman spectra.

Synthesis, crystal structure, and biological activity of a Pt-dipyridamole salt

In the present paper we present data on the synthesis, crystal structure and biological activity of bis(dipyridamole) tetrachloroplatinate(II).dipyridamole.dihydrate, [dpmH]2 PtCl4.dpm.2H2O. The crystals are Triclinic P1 with a = 11.490(2) A, b = 13.630(2) A, c = 15.81(1) A, a = 100.97(2) degrees, beta = 100.89(3) degrees, gamma = 112.35(1) degrees, Z = 1, M = 1885.9, Dx = 1.46 g/cm3, MoK alpha (lambda = 0.71069 A), mu = 0.0184 mm-1, R = 4.4%, Rw = 5.0%, 3231 (1 > 2 sigma (I)). The structure is stabilized by a hydrogen-bonding network. It was observed that although dpm alone is not able to alter the electrophoretic mobility of pUC8 DNA forms, the synthesized Pt-dpm compound substantially modifies the DNA conformation since it significantly alters the electrophoretic mobility of nicked and closed circular forms of pUC8 DNA. However, the alteration in mobility of pUC8 DNA induced by this compound upon binding is lower than that induced by cis-DDP. The analysis of the antiproliferative activity of the Pt-dpm salt against MDA-MB 468 (breast carcinoma) and HL-60 (leukemia) human cancer cells showed that this compound has ID50 values of 0.87 microM and 0.65 microM, respectively. Interestingly, it was found out that although the dpm molecule does not present any significant antiproliferative activity, the ID50 values of Pt-dpm are about 3-fold and 7-fold lower than those of cis-DDP and K2PtCl4, respectively. Altogether the biological data suggest that in Pt-dpm a synergic effect between cation and anion is produced.

Orthometalation reactions of substituted benzylideneamines by palladium(II) chloride

Abstract Carbonmetal σ-bonded complexes have been synthesized by reaction of various substituted benzylideneamines with PdCl 2 . The chloro-bridged complexes formed have been studied by spectroscopic methods and by thermogravimetric analyses.