Małgorzata Latocha

Structure, properties and cytostatic activity of tributyltin aminoarylcarboxylates

Abstract Properties of butyltin complexes [Sn(C4H9-n)3{OOCC6H3(NH2)2-3,4}]n (1), [Sn(C4H9-n)3{OOCC6H3(NH2)2-3,5}] (2), [Sn(C4H9-n)3{OOCC6H4NNC6H4N(CH3)2-4}] (3) and [Sn(C6H5)3{OOCC6H3(NH2)2-3,5}]n (4) have been investigated. 1H, 13C and 119Sn NMR spectra indicate that the compounds in chloroform are distorted tetrahedral and in strongly coordinating solvents trigonal-bipyramidal complexes. Structure of complex 3 has been determined by X-ray crystallography. This compound adopts trigonal bipyramidal structure with bridging carboxylato ligand bound asymmetrically with tin atoms in axial positions. The complexes are effective cytostatic agents.

Structure, Properties and Cytostatic Activity of Triorganotin (Aminoaryl)carboxylates

The properties of vinyltin and phenyltin complexes [Sn(CH=CH2)3{μ-OOCC6H3(NH2)2-3,4}]n (1), [Sn(C6H5)3{OOCC6H3(NH2)2-3,4}] (2), [Sn(C6H5)3{OOC-2-C6H4N=NC6H4N(CH3)2-4}] (3) and [Sn(CH=CH2)3{OOC-2-C6H4N=NC6H4N(CH3)2-4}] (4) have been investigated. The structures of complexes 1, 2, and 3, have been determined by X-ray crystallography. Compound 1 is a distorted trigonal-bipyramidal complex and compounds 2 and 3 adopt a distorted tetrahedral structure. Complex 1 is a single-strand polymer with a bridging 3,4-diaminobenzoato ligand coordinating via the O(1) atom of the carboxylato group and the nitrogen atom of the para-amino group. The oxygen and nitrogen atoms occupy the axial coordination sites. The Sn(1)−N(2A) bond is weak. In complexes 2 and 3 the carboxylato ligands are strongly coordinated to the central atom via one oxygen atom, and the Sn(1)−O(2) distances are considerably longer. Weak interactions of the central atom with the amino group in complex 1, and with the O(2) atoms in complexes 2 and 3, as well as the hydrogen bonds, stabilize the crystal structure. The complexes are effective cytostatic agents. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Pyrolytic GC-MS analysis of melanin from black, gray and yellow strains of Drosophila melanogaster

Abstract Properties of melanins depend strongly on their chemical constitution. Melanins from differently colored strains of Drosophila melanogaster demonstrate various proprieties, and biological activity in the presence of toxic ions or radiation. In the presented work, we analyzed chemical constitution of the melanins derived from black, gray and yellow D. melanogaster strains. Analysis of the products forming during thermal degradation of the biopolymers by pyrolitic gas chromatography followed by mass spectrometry allowed us to determine chemical composition of these biopolymers and classified melanins derived from black and gray strains as eumelanins and derived from yellow strains as pheomelanins. These findings allow us to determine chemical and biological properties of the melanins in vivo, and can explain susceptibility of differently colored strains of D. melanogaster to metal ions.

Structure, properties and in vitro cytotoxic activity of hexakis(2-cyanoethyl)ditin(III).

The structure of the tin(III) complex [Sn(2)(CH(2)CH(2)CN)(6)] has been determined. There are two independent molecules in the crystal, both adopt distorted eclipsed conformation. The molecular and electronic structures of this compound have been studied both at the semiempirical level and with the use of non-empirical ab initio methods. The calculated Sn-Sn distances agree well with those found crystallographically. The results of calculations showed that the eclipsed conformation of complex is more stable as compared with staggered conformation. The compound show modest cytotoxic activity against A549 and HSMC cells.

Butyltin(IV) 2-sulfobenzoates: Synthesis, structural characterization and their cytostatic and antibacterial activities

Three butyltin complexes with 2-sulfobenzoic acid [Sn(C(4)H(9))(2){O(3)SC(6)H(4)COO-2}(H(2)O)]·(C(2)H(5)OH) (1), [Sn(C(4)H(9))(3){O(3)SC(6)H(4)COOH-2}] (2) and [Sn(2)(C(4)H(9))(6){μ-O(3)SC(6)H(4)COO-2}] (3) have been synthesized and characterized by IR and (1)H, (13)C and (119)Sn NMR spectra. They show interesting properties in solid state and solutions because there are many modes of coordination of the Sbz ligand. The structure of complex 1 has been determined by X-ray crystallography. It is a chain compound with 2-sulfonatobenzoate coordinated to Sn atoms as a bridging and chelate ligand via O atoms of COO and SO(3) groups. In solutions the chains dissociate giving mainly mononuclear complexes. The NMR spectra and calculation at the DFT B3LYP/3-21G** level indicate that in solutions of compounds 1, 2 and 3 in polar solvents, many complexes showing dynamic properties are formed. Density functional theory (DFT) calculations showed that many five- and six-coordinate isomers and conformers can exist in equilibrium. All compounds effectively interact with AMP and ATP. The NMR spectra showed that nucleotides are coordinated to Sn atoms via PO(4) groups. The complexes are very active cytostatic agents against tumor strains. They are more effective than cisplatin. It is interesting that activity of 3 against non-tumor cell NHDF is lower than against tumor cells. Antibacterial activity of 1 and 2 has been investigated. Compound 2 is a very effective agent against Gram-positive bacteria. Antibacterial activity of 1 is lower than that of 2. Activity of 1 both against Gram-positive and Gram-negative bacteria is similar.

Effect of oxygen on spin-spin and spin-lattice relaxation in DOPA-melanin. Complexes with chloroquine and metal ions

Electron paramagnetic resonance (EPR) studies of complexes of chloroquine with melanin synthesized from 3,4-dihydroxyphenylalanine (DOPA) confirmed an important role ofo-semiquinone free radicals during the drug binding by melanin. Chloroquine increases free radical concentration in DOPA-melanin. It has been also demonstrated that chloroquine binding to melanin is modified by metal ions. Co2+ ions reduce and Zn2+ ions increase the concentration of free radicals in both DOPA-melanin and melanin-chloroquine complexes. Free radical properties of melanin strongly depend on the presence of oxygen (O2) in the environment of the sample. Interactions of melanin and oxygen molecules cause a decrease of the free radical concentration in the samples and a narrowing of the EPR lines. Higher values of both spin-spin and spin-lattice relaxation times were determined for melanin samples in air than for evacuated samples. Application of the observed effects in oximetry is suggested.

Vitamin D analogs decrease in vitro secretion of RANTES and enhance the effect of budesonide.

PURPOSE Eosinophils appear to be central inflammatory cells in the pathogenesis of rhinosinusitis with nasal polyps (NP). One of the most predominantly recognized eosinophil chemoattractants is RANTES. The aim of this study was to assess the influence of vitamin D (VD) derivates on RANTES expression in the culture of nasal polyp fibroblasts. MATERIAL AND METHODS NP fibroblast cell cultures derived from 16 patients with NP were first stimulated with bacterial LPS and than incubated in increasing concentrations (from 10(-7)M to 10(-4)M) of calcitriol, tacalcitol or budesonide and in combination with one of VD derivate with budesonide in 1:1, 1:3 and 3:1 ratios. Quantitative analysis of RANTES level was conducted in culture supernatants using an ELISA method. RESULTS The highest calcitriol concentration (10(-4)M) as well as tacalcitol at 10(-5)M and 10(-4)M reduced RANTES production significantly compared to the control (201.1pg/ml, 338.7pg/ml, 211.3pg/ml v 571.78pg/ml; p<0.05). Budesonide and calcitriol administered in 1:3 ratio and budesonide and tacalcitol in 1:1 and 1:3 reduced RANTES concentration significantly better than each of the drug used in monotherapy (p<0.05). Budesonide and tacalcitol in 1:1 and 1:3 ratios suppressed RANTES production to the lowest level (171.8±97.6pg/ml and 178.7±105.22pg/ml, respectively). CONCLUSION Active VD compounds via downregulation of RANTES production exert a potential role as a complementary element in the therapy of chronic rhinosinusitis with NP. Compounds consisting of budesonide and VD derivate have an advantage over both drugs used in monotherapy.

Synthesis, molecular docking study, and evaluation of the antiproliferative action of a new group of propargylthio- and propargylselenoquinolines

This study describes the synthesis of a new group of halogenopropargylthio-, dipropargylthio-, and halogenopropargylseleno-quinoline derivatives. The ability of all of the synthesized compounds to inhibit the proliferation of the T-47D, MCF-7, MDA-MB-231, and SNB-19 cell lines was determined with the WST-1 assay. The normal fibroblast cell line (HFF-1) was used as a control. The cytotoxic properties of these new, modified propargylquinoline derivatives were comparable to those of cisplatin. The most active compounds, 4,7-dipropargylthiquinoline (8b) and 7-chloro-4-propargylselenoquinoline (5b), were docked into the binding site of human CYP1A1 and CYP1B1. Our data indicate that these derivatives may present promising chemotherapeutic agents, possibly targeting CYP1s pathway.

Effect of depth on radiation-induced cell damage in a water phantom

Summary Aim The paper describes the effect of medium depth on radiation-induced genetic damage to SK-mel cultured cells placed inside a water phantom as measured by the number of cells with micronuclei formed and apoptoses seen in these cells. Materials/Methods The energy of photon radiation used was 6 MV; cells placed at various depths were irradiated with the same dose (5 Gy). Results/Conclusions Depending on medium depth, differences were noted in the number of damaged cells: ca.30% more affected cells were seen at a depth of 25 cm as compared to a depth of 5 cm. With increasing depth also the radiation energy spectrum changes. This is probably responsible for the observed effect. It should be taken into consideration in both clinical practice and in treatment planning.

Effect of Zn2+ and Cu2+ on free radical properties of melanin fromCladosporium cladosporioides

Effect of metal ions on free radical properties of natural melanin produced by soil fungiCladosporium cladosporioides was studied. The electron paramagnetic resonance (EPR) spectrum of the studied melanin consists mainly of a single line of eumelanin, and only a very weak signal of pheomelanin was observed. o-Semiquinone free radicals form paramagnetic centers in melanin. Diamagnetic Zn2+ ions produce an increase in the free radical concentration in melanin. Quenching of melanin EPR lines was obtained for melanin and paramagnetic Cu2+ ion complexes. Slow spin-lattice relaxation processes are characteristic for the free radicals in melanin samples and fast spin-lattice relaxation was observed for Cu2+ ions. The EPR lines of copper ions saturate at higher microwave powers than the EPR lines of melanin.