Monothioacids as novel chelating groups. The Au(III) complexes of N-methylthioamide monothiooxamic acid.

CH3HNCSCSOH(LH) forms AuLCl2, AuLBr2, AuL2Cl and AuL2Br complexes in acid media. The complexes are characterised by their elemental analysis and the vibrational spectra. A thorough analysis of the vibrational spectra is carried out to reveal the structure of these complexes. From this study we could conclude that all complexes exhibit a square-planar geometry around the metal ion and that in all cases the ligand acts as a bidentate, coordinating through the sulphur atoms of the thioamide and monothioacid functional groups, forming chelate ring systems.

Synthesis and biological evaluation of dihydrobenzofuran lignans and related compounds as potential antitumor agents that inhibit tubulin polymerization.

A series of 19 related dihydrobenzofuran lignans and benzofurans was obtained by a biomimetic reaction sequence involving oxidative dimerization of p-coumaric, caffeic, or ferulic acid methyl esters, followed by derivatization reactions. All compounds were evaluated for potential anticancer activity in an in vitro human disease-oriented tumor cell line screening panel that consisted of 60 human tumor cell lines arranged in nine subpanels, representing diverse histologies. Leukemia and breast cancer cell lines were relatively more sensitive to these agents than were the other cell lines. Compounds 2c and 2d, but especially 2b (methyl (E)-3-¿2-(3, 4-dihydroxyphenyl)-7-hydroxy-3-methoxycarbonyl-2, 3-dihydro-1-benzofuran-5-ylprop-2-enoate), the dimerization product of caffeic acid methyl ester, containing a 3',4'-dihydroxyphenyl moiety and a hydroxyl group in position 7 of the dihydrobenzofuran ring, showed promising activity. The average GI(50) value (the molar drug concentration required for 50% growth inhibition) of 2b was 0.3 microM. Against three breast cancer cell lines, 2b had a GI(50) value of <10 nM. Methylation, reduction of the double bond of the C(3)-side chain, reduction of the methoxycarbonyl functionalities to primary alcohols, or oxidation of the dihydrobenzofuran ring to a benzofuran system resulted in a decrease or loss of cytotoxic activity. Compound 2b inhibited mitosis at micromolar concentrations in cell culture through a relatively weak interaction at the colchicine binding site of tubulin. In vitro it inhibited tubulin polymerization by 50% at a concentration of 13 +/- 1 microM. The 2R, 3R-enantiomer of 2b was twice as active as the racemic mixture, while the 2S,3S-enantiomer had minimal activity as an inhibitor of tubulin polymerization. These dihydrobenzofuran lignans (2-phenyl-dihydrobenzofuran derivatives) constitute a new group of antimitotic and potential antitumor agents that inhibit tubulin polymerization.

Synthesis and antiviral activity of 7-O-(omega-substituted)-alkyl-3-O-methylquercetin derivatives.

3',4'-Di-O-benzyl-3-O-methylquercetin (2), the precursor in the synthesis of an important antivirally active flavone 3-O-methylquercetin (1), was regioselectively alkylated at the 7-OH position by a series of 1,omega-dihaloalkanes and omega-bromoalkanols. Dimerization of the flavone had to be avoided by applying strict reaction conditions. Subsequent debenzylation was carried out by catalytic transfer hydrogenolysis, affording quantitatively the 7-O-(omega-haloalkyl)-3-O-methylquercetin (11-14) and 7-O-(omega-hydroxyalkyl)-3-O-methylquercetin derivatives (15, 16). All compounds were tested for their antiviral activity against poliomyelitis- and HIV-viruses.

Anti-HIV activity of flavonoids and proanthocyanidins from Crataegus sinaica.

In addition to quercetin, hyperoside, rutin, vitexin, 2″-O-rhamnosylvitexin, (4″'-O-acetyl)-2″-O-rhamno-sylvitexin, epicatechin, procyanidin B-5, proanthocyanidin A-2, procyanidin B-2 and procyanidin C-1, which were reported before in Crataegus sinaica (Rosaceae), three more flavonoids were isolated from the same plant, i.e. (+)-taxifolin, 3-O-ß-arabinopyranosyl-(+)-taxifolin and 3-0-ß-xylopyranosyl-(+)-taxifolin. The in vitro anti-HIV activity of some selected flavonoids and proanthocyanidins was evaluated. The dimeric procyanidin B2 and proanthocyanidin A2, and especially the trimeric procyanidin C1 showed some in vitro anti-HIV activity.

High resolution NMR imaging: Gd-DTPA labeled enzyme as a probe for permeability studies in polyacrylamide gels.

The penetration of horse liver alcohol dehydrogenase (HLAD) molecules into polyacrylamide gel beads, which are used to immobilize the enzyme, was studied. HLAD was labeled with gadolinium diethylene-triamine-pentaacetic acid (Gd-DTPA), using the N-hydroxy-succinimide active ester of DTPA as a chelating agent. The HLAD-(Gd-DTPA)27 has a 3.7-fold larger longitudinal (R1) and a 14-fold larger transversal relaxivity (R2) (at 2.4 T) than the plain Gd-DTPA. A series of dry polyacrylamide gel beads, with total monomer concentration ranging from 5% to 30% were synthesized and swollen in a buffered solution of HLAD-(Gd-DTPA)27. The gel beads were examined with high resolution NMR imaging. The T1- and T2-weighted images revealed that the permeability for the labeled HLAD decreased with increasing total monomer concentration of the gel beads. These imaging results correlate fairly well with the enzymatic reactivities measured for the same range of gel beads but swollen in a solution of non labeled HLAD and NAD+ (nicotinamide adenine dinucleotide). It is concluded that Gd-labeling can be used to monitor the distribution of weakly concentrated, water soluble products in a solid matrix.

Isolation and identification of 2-oxo-5-guanidinovaleric acid in urine of patients with hyperargininaemia by chromatography and gas chromatography/mass spectrometry.

An unknown guanidino-positive peak has been identified in urines of three sisters affected with hyperargininaemia. Identification was made on the basis of its similarity with the liquid and thin-layer chromatographic characteristics of enzymatically synthesized 2-oxo-5-guanidinovaleric acid. Identification was also made by combined gas chromatography-mass spectrometry of the unknown compound peak. The synthesis of enzymatically formed 2-oxo-5-guanidinovaleric acid was controlled by nuclear magnetic resonance and combined gas chromatography-mass spectrometry.

Reduction of cycloalkanones by Aspergillus niger.

The mould Aspergillus niger was grown in a carefully established culture medium containing one of the following test substrates: cyclopentanone, -hexanone, -heptanone, and their 2-substituted methyl derivatives. Growth curves, glucose consumption curves and curves showing the course of the oxido-reduction reaction are given.