Metal complexes of retinoid derivatives with antiproliferative activity: synthesis, characterization and DNA interaction studies.

9-cis-Retinal thiosemicarbazone and its Co(III), Ni(II) and Cu(II) complexes are synthesized and characterized. Central Co(III) atom is in an octahedral environment while Ni(II) and Cu(II) atoms are in a square planar environment. DNA binding constants and spectroscopic data show an intercalative behavior for the nickel complex; an external binding mode is envisaged for the ligand and its copper complex. No DNA interaction can be hypothesized for the cobalt complex. The free ligand and its Ni(II) and Cu(II) complexes have a good lipophilic degree for an efficient uptake by the cells. The metal complexes exhibit a proliferation inhibition action against cell line U937 at micromolar concentration. Cu(II) complex also induces apoptosis, while Ni(II) complex has a strong interaction with CT-DNA.

Sodium 2-oxo-3-semicarbazono-2,3-dihydro-1H-indole-5-sulfonate dihydrate.

The title compound, Na+.C9H7N4O5S-.2H2O, presents a Z configuration around the imine C=N bond and an E configuration around the C(O)NH2 group, stabilized by two intramolecular hydrogen bonds. The packing is governed by ionic interactions between the Na+ cation and the surrounding O atoms. The ionic unit, Na+ and 2-oxo-3-semicarbazono-2,3-dihydro-1H-indole-5-sulfonate, forms layers extending in the bc plane. The layers are connected by hydrogen bonds involving the water molecules.

Isatin 3-semicarbazone and 1-methylisatin 3-semicarbazone.

The two title semicarbazones, namely 2,3-dihydro-1H-indole-2,3-dione 3-semicarbazone, C9H8N4O2, (I), and 1-methyl-2,3-dihydro-1H-indole-2,3-dione 3-semicarbazone, C10H10N4O2, (II), show the same configuration, viz. Z around the imine C=N bond and E around the C(O)-NH2 bond, stabilized by two intramolecular hydrogen bonds. The presence of a methyl group on the isatin N atom determines the difference in the packing; in (I), the molecules are linked into chains which lie in the crystallographic (102) plane and run perpendicular to the b axis, while in (II), the molecules are arranged to form helices running parallel to a crystallographic screw axis in the a direction.

New methyl pyruvate thiosemicarbazones and their copper and zinc complexes: synthesis, characterization, X-ray structures and biological activity.

By reacting thiosemicarbazides substituted on the aminic nitrogen with both alkyl or aryl groups, and methyl pyruvate a new group of methylpyruvate thiosemicarbazones (Hmpt) derivatives was obtained. These ligands were then treated with copper and zinc inorganic salts. All isolated compounds were characterized using spectroscopic methods. The single crystal structural analysis of the ligands Me-Hmpt x 0.5H2O 1, Et-Hmpt x H2O 2, Ph-Hmpt 5, Meph-Hmpt 6 showed that only compound 6 presents significant deviation from planarity. The X-ray structure of [Zn(Me-Hmpt)Cl2] x H2O 8 showed that in this complex Me-Hmpt behaves as a neutral ligand SNO terdentate and that the penta coordination is achieved by chloride ions according to spectroscopic and elemental analyses. On the basis of the analytical data the same behavior is proposed for the other zinc complexes. All the ligands in copper complexes seem to be monodeprotonated; nevertheless the same SNO behavior is expected. Tests on cell proliferation of human leukemic cell line U937 showed that the copper complex Cu(Et-mpt)Cl x H2O is the most active compound among those reported even though it is not able to induce apoptosis.

Transition-metal complexes of isatin-beta-thiosemicarbazone. X-ray crystal structure of two nickel complexes.

Manganese, iron, cobalt, nickel, copper and zinc complexes of isatin-beta-thiosemicarbazone (H2L) have been synthesized and spectroscopically characterized The X-ray crystal structures of two nickel complexes, namely [Ni(HL)2]. EtOH (1) and [Ni(HL)2]. 2DMF (2), reveal a distorted octahedral coordination with the monodeprotonated ligand that behaves as an O,N,S terdentate. Different packing interactions are determined by the presence of different crystallization solvents, i.e., ethanol in 1 and dimethylformamide (DMF) in 2. 1H and 13C NMR studies of the ligand and zinc complexes in solution were carried out and a complete assignment for the ligand was made by homodecoupling, gradient assisted 2D 1H-13C HMQC and HMBC NMR spectroscopy. Biological studies, carried out in vitro on human leukaemic cell lines U937, have shown that the free ligand and the copper (II) complex are more active in the inhibition of cell proliferation than the nickel complexes. No compound was able to induce apoptosis.

Acenaphthenequinone thiosemicarbazone and its transition metal complexes: synthesis, structure, and biological activity.

The reaction of iron, nickel, copper, and zinc chlorides or acetates with acenaphthenequinone thiosemicarbazone, Haqtsc leads to the formation of novel complexes that have been characterized by spectroscopic studies (NMR, IR) and biological properties. The crystal structures of the free ligand Haqtsc 1 and of the compound [Ni(aqtsc)2].DMF 2, have also been determined by X-ray methods from diffractometer data. In 1, the conformation of the two nonequivalent molecules is governed by intramolecular hydrogen bonds, while an intermolecular hydrogen bond is responsible for dimer-like groups formation. In 2, the coordination geometry about nickel is distorted octahedral, and the two ligand molecules are terdentate monodeprotonated. Biological studies have shown that, for the first time at least up the used doses, a free ligand is active both in the inhibition of cell proliferation and in the induced differentiation on Friend erythroleukemia cells (FLC).

2,6-diacetylpyridine bis(thiosemicarbazones) zinc complexes: synthesis, structure, and biological activity.

The reaction of zinc chloride, acetate, or perchlorate with two bis(thiosemicarbazones) of 2,6-diacetylpyridine [H2daptsc = 2,6-diacetylpyridine bis(thiosemicarbazone) and H2dapipt = 2,6-diacetylpyridine bis(hydrazinopyruvoylthiosemicarbazone)] leads to the formation of four novel complexes that have been characterized by spectroscopic studies (NMR, IR) and biological properties. The crystal structures of the two compounds--[Zn(daptsc)]2.2DMF (1) and [Zn(H2dapipt)(OH2)2](CIO4)2.3H2O (2)--also have been determined by x-ray methods from diffractometer data. Compound (1) is dimeric and the two zinc atoms have a distorted octahedral coordination. The ligand is deprotonated. In compound (2), the coordination geometry about zinc is pentagonal--bipyramidal and the ligand is in the neutral form. The molecular structure of (2) consists of cations [Zn(H2dapipt)(OH2)]2+, CIO4- disordered anions, and three water molecules of solvation. Biological studies have shown that the ligands and the complexes Zn(daptsc).1/2EtOH and Zn(H2daptsc)Cl2 have an effect in vitro on cell proliferation and differentiation (inhibition); both are concentration dependent. [Zn(daptsc)]2.2DMF (1) shows the effects at lower concentration values with respect to other compounds.

Synthesis, spectroscopic and structural characterization, and biological activity of aquachloro (pyridoxal thiosemicarbazone) copper(II) chloride.

The synthesis, spectroscopic studies, x-ray crystal structure, and biological properties of the complex [Cu(H2L)(OH2)Cl]Cl (1) (H2L = pyridoxal thiosemicarbazone) are reported. The compound crystallizes in space group P2(1)/n, a = 12.128(2), b = 9.096(2), c = 13.592(2) A, beta = 108.65(2) degrees, U = 1420.7 A3, and Z = 4. The molecular structure consists of discrete cations [Cu(H2L)(OH2)Cl]+ and Cl- anions. Each copper atom is in an approximately square pyramidal environment involving the phenolic oxygen, the imine nitrogen, the sulphur, and a water oxygen in the equatorial positions, while a chlorine atom occupies the axial position. The structure of this complex is compared to that of the dimeric [(Cu(HL)(OH2))2]Cl2.2H2O (2) obtained under different experimental conditions, to that of a Co(III) complex with the same ligand [Co(HL)L].4.5H2O (3) and to that of the free ligand H2L, especially in relation to its biological activity. Compounds 1 and 2 have not antiviral action in vitro with respect to RNA viruses, show an inductive effect on Friend erythroleukemia cells (FLC), erythroid differentiation and a suppressive effect regarding FLC proliferation. Complex 3 and the free ligand do not have biological activity.