Juan L. Manzano

Thiourea derivatives and their nickel(II) and platinum(II) complexes: antifungal activity

We have synthesized two thiourea derivatives of methyl anthranilate (1, 2) and their complexes with nickel (3) and platinum(II) (4). We have also prepared the complexes of nickel(II) with two benzoylthiourea derivatives (5, 6). The obtained compounds were characterized by elemental analysis, spectroscopic methods (FT-IR, UV-vis, NMR), mass spectrometry and thermal analysis. Compound 1, C(20)H(23)N(3)O(2)S, crystallizes in monoclinic space group P21/n, with Z=4, and unit cell parameters, a=8.8042(4) A, b=7.6608(3) A, c=28.834(2) A, alpha=gamma=90 degrees, beta=90.94(1) degrees. Compound 2, C(20)H(21)N(3)O(3)S, crystallizes in monoclinic space group P21/c, with Z=4, and unit cell parameters, a=7.7345(4) A, b=8.6715(4) A, c=29.113(2) A, alpha=gamma=90 degrees, beta=90.67(1) degrees. Compound 5, C(24)H(30)N(4)NiO(2)S(2), crystallizes in monoclinic space group P21/n, with Z=4, and unit cell parameters, a=10.4317(8) A, b=18.517(2) A, c=13.299(1) A, alpha=gamma=90 degrees, beta=104.53(1) degrees. Compound 6, C(25)H(28)Cl(2)N(4)NiO(4)S(2), crystallizes with a molecule of CH(2)Cl(2) in triclinic space group P-1, with Z=2, and unit cell parameters, a=10.362(1) A, b=11.849(2) A, c=12.536(2) A, alpha=90.04(2) degrees, beta=84.73(1) degrees, gamma=113.43(2) degrees. Compounds 1 and 2 show antifungal activity against the major pathogens responsible for important plant diseases (Botrytis cinerea, Colletotrichum fragariae, Fusarium oxysporum and Phoma betae). The antifungal activity is practically the same for morpholine and ethyl derivatives.

New organotropic compounds. Synthesis, characterization and reactivity of Pt(II) and Au(III) complexes with bile acids: DNA interactions and 'in vitro' anticancer activity.

Based on the ability of bile acids to vectorialize the cytostatic activity of other agents, we have designed and synthesized a new series of platinum and gold complexes. These compounds were studied and characterized by elemental analysis, FT-IR, FAB(+)/MS, 1H, 13C and 195Pt NMR, UV-Vis spectroscopy and conductivity measurements in solution, among other techniques. Kinetic studies carried out in aqueous solution and in the presence of different NaCl concentrations: 4 mM (similar to cytoplasmic concentration), 150 mM (similar to plasmatic concentration). The effects on the electrophoretic mobility of the pUC18 plasmid, the DNA denaturation temperature, and ethidium bromide (EtBr) binding to DNA were studied. The complexes are able to inter-react with DNA to inhibit DNA synthesis and hence, to reduce cell proliferation. The complexes were evaluated for in vitro cytostatic activity against human colon adenocarcinoma, mouse hepatoma, human hepatoma, mouse leukemia, etc. The antitumor effect of some of the compounds prepared was similar to that of cisplatin. However, other compounds had lower cytostatic activity. This different behavior can be accounted for by the structure/activity relationship (SAR), although other factors, such as uptake and the different kinetic behavior in solution, may be responsible for these differences.

Structural characterization and cytostatic activity of chlorobischolylglycinatogold(III).

Based on the ability of bile acids for vectorializing the cytostatic activity of other agents, we have designed and synthesized a new bile acid cholylglycinato Au(III) complex, named Bamet-A1. It has been characterized by means of EA (elemental analysis), FT-IR, NMR, FAB-MS (fast atom bombardment-mass spectrometry) and Vis-UV techniques. This characterization allowed us to propose a structure of the type [Au CG(O) CG(N,O) Cl] for the neutral complex, which has the composition C522H84N2O12AuCl and is very soluble in water, methanol, ethanol and DMSO (dimethylsulfoxide). The study in aqueous solution suggested a redox process for its transformation, which is accompanied by the appearance of colloidal gold phase. The behavior in 4 mM NaCl water (in order to mimic the cytoplasmatic fluid) was similar to that observed in water, while in a 150 mM NaCl (similar to extracellular fluid and serum), the apparition of a dark blue precipitate was observed. This complex displays fluorescence, which does not change when incubated with DNA obtained from E. coli. Bamet-A1 was found to inhibit the growth of a variety of cell lines. The cytostatic effect was mild against human hepatoma HepG2, mouse hepatoma Hepa 1-6, rat hepatoma McA RH-7777 and human colon adenocarcinoma LS-174T, and stronger against mouse sarcoma S180-II and mouse leukemia L-1210 cells. The appearance of colloidal Au during the process of hydrolysis under physiological conditions may explains the low cytostatic activity.

Bisursodeoxycholate(ethylenediamine)platinum(II): a new autofluorescent compound. Cytotoxic activity and cell cycle analysis in ovarian and hematological cell lines.

The present paper describes for the first time an intrinsic fluorescent square-planar platinum(II) complex carrying two ursodeoxycholate ligands ([Pt(UDC)2(en)], where UDC(-) = ursodeoxycholate), that emits at room temperature once free in solution. Kinetic studies were carried out in aqueous solution and in the presence of different NaCl concentrations: 4 mM (similar to cytoplasmic concentration) and 150 mM (similar to plasmatic concentration). This novel compound was synthesized from a [PtCl2(en)] complex and shows increased cytotoxic activity against both resting and cycling HeLa cells, with no toxicity for cell lines derived from neoplastic haematopoietic cells.

Preparation and characterization of a copper(II) compound with a new glycine Schiff base containing an ester function

SummaryA new Schiff base was obtained from glycine and ethyl-α-ketocyclopentylcarboxylate. This forms a potassium salt K(Rgly)·H2O, where Rgly=C10H14O4N. From this salt a new copper(II) complex was prepared, Cu(Rgly′)·2H2O, where Rgly′=C10H13O4N (deprotonated Schiff base). The compounds were characterized by i.r. spectroscopy, differential thermal analysis (d.t.a.) and thermogravimetric analysis (t.g.). The activation energy corresponding to the dehydration process for compounds was determined. On the basis of spectral data, the copper compound is believed to be pentacoordinate and square pyramidal.

New Fluorescent Antitumour Cisplatin Analogue Complexes. Study of the Characteristics of their Binding to DNA by Flow Injection Analysis

The flow injection technique is applied to study the binding to DNA of new platinum complexes—E1: ethylenediaminechlorocholylglycinateplatinum(II): [PtCl(CG)(en)], C54H92O12Pt and E2: ethylenediaminebischolylglycinateplatinum(II): [Pt(CG)2(en)], C28H50ClN3O6Pt—derived from cisplatin in which the exchangeable ligands were replaced by bile acids, such that these anticancer drugs have less toxicity and less resistance is developed towards them. Both compounds are fluorescent and their fluorescence is enhanced when they form adducts with DNA, a property that is extremely useful for monitoring the cytotoxic activity and their mechanisms of action. The binding parameters to DNA of E1 [apparent intrinsic binding constant KE1: (11.2 ± 0.4) × 103 M−1 and maximum number of binding sites per nucleotide, nE1: 0.121 ± 2 × 10−3) and E2 (KE2: 9.2 ± 0.7) × 103 M−1 and nE2 0.098 ± 2 × 10−3] were determined following the Scatchard method and the type of binding was studied experimentally through the modifications introduced by each of the compounds into the ethidium bromide–DNA bond.

Some Lanthanide Complexes of a Glycine Derivative Containing an Ester Function

Abstract Lanthanide complexes: Ln(Rgly)2OH2 H2O (where Ln = La-Ho and Y: Rgly = C10H14O4N) have been prepared by the reaction of the corresponding lanthanide chloride and the ligand N-(2-ethoxycarbonyl-l-cyclopent-en-yl)-glycinate (Rgly). The complexes were characterized by elemental analysis, electrical conductance. magnetic susceptibility, IR and UV-visible spectra and thermal analysis.

Preparation and thermal study of the potassium, magnesium, calcium and barium compounds with an l-alanine derivative containing an ester function

Abstract The compounds K(Rala)·H 2 O and M(Rala) 2 · n H 2 O (M = Mg, n = 4; M = Ca and Ba, n = 2; Rala = C 11 H 16 NO 4 − ), obtained by condensation reaction between ethyl-α-ketocyclopentylcarboxylate (C 8 H 12 O 3 ) and the L-alanine in the presence of the metallic salt, have been prepared and studied. The compounds are characterized by elemental analysis, by IR, UV and mass spectroscopy, NMR and thermal analysis (TG, DTA and DSC).

Preparation and thermal study of the magnesium, calcium and barium compounds with a glycine Schiff base containing an ester function

Abstract The compounds N[Rgly]2·nH2O (M = Mg and Ca, n = 4; M = Ba, n = 2; Rgly− = C10H14NO4−), obtained by the condensation reaction between ethyl-α-ketocyclopentylcarboxylate and glycine in the presence of the metallic salt, were prepared and studied. The compounds were characterized by IR and UV spectroscopy, differential thermal analysis and thermogravimetric analysis.

Stabilization of Nickel(II) Chlorocomplexes with α,ω-Alkanediammonium Cations

Abstract The following nickel(II) chlorocomplexes stabilized with α,ω alkanediammonium cations were prepared: NiCl2·2bnH2Cl2·5H2O (1), 2NiCl2·2pnH2Cl2·4H2O (2), 2NiCl2·hnH2Cl2·4H2O (3), 2NiCl2·2hpH2Cl2·4H2O (4), where bn = 1,4-butanediamine, pn = 1,5-pentanediamine, hn = 1,6-xanediamine and hp = 1,7-heptanediamine. The solid state electronic spectra and magnetic moments show that nickel (II) is octahedral in all the compounds. The complex anion can be formulated as [Ni2Cl6(H2O)4]2− for compound (3), [Ni2Cl8(H2O)2]4- for compounds (2) and (4) and [NiCl4(H2O)2]2- for compound (1). By loss of water molecules the corresponding anhydrous compounds are produced; these apparently contain the dimer species with pentacoordinated nickel [Ni2Cl8]4-. The anhydrous compound obtained from (3) contains the polymeric species with hexacoordinated nickel [NiCl3]n- n.