Inhibitory effect of some acetyl esters and acetamides on glycation of the histone H1.

Non-enzymatic glycosylation (glycation) is a spontaneous set of reactions between reducing sugars and free amino groups in proteins or other biomolecules leading to the formation of fluorescent and coloured compounds known as advanced glycation end products (AGEs). AGEs cause structural changes of key proteins in humans, and therefore they are related with a number of physiological processes and diseases such as aging, atherosclerosis, cataract, arthritis, Alzheimer's disease. Two main strategies have been employed to prevent the formation of AGEs: a) low carbohydrate diet and b) pharmacological intervention.

Genotoxic effect of 4-aroyl-1-(2-chloroethyl)-1nitrosohydrazinecarboxamides on Saccharomyces cerevisiae cells.

The study of some 4-aroyl-1-(2-chloroethyl)-1-nitrosohydrazinecarboxamides with a Saccharomyces cerevisiae mutagenicity test of increased sensitivity defined two of them, 4-(4-bromobenzoyl)-1-(2-chloroethyl)-1-nitrosohydrazinecarboxam ide and 4-(4-fluorophenyl)-1-(2-chloroethyl)-1-nitrosohydrazine carboxamide as typical cytostatic agents. At concentrations of 2-5 microg/ml the substances kill up to 60%-70% of cells without having any detectable recombinogenic and mutagenic effects. At the same concentrations, lomustine, well known as a cytostatic reference, demonstrated recombinogenic and mutagenic activity on yeast cells.

Synthesis and antitumour activity of several new 4-aroyl-1-nitrosohydrazinecarboxamides.

Six new analogues of nitrosoureas containing aroylhydrazine residue have been synthesized: (I) 4-(2-fluorobenzoyl)-1-(2-chloroethyl)-1-nitrosohydrazinecarboxamide++ +; (II) 4-(4-bromobenzoyl)-1-(2-chloroethyl)-1-nitrosohydrazinecarboxam ide; (III) 4-(4-hydroxybenzoyl)-1-(2-chloroethyl)-1-nitrosohydrazinecarboxamide+ ++; (IV) 4-(3-methoxybenzoyl)-1-(2-chloroethyl)-1-nitrosohydrazinecarbox amide; (V) 4-(4-methoxybenzoyl)-1-(2-chloroethyl)-1-nitrosohydrazinecarbox amide; (VI) 4-(4-fluorophenylacetyl)-1-(2-chloroethyl)-1-nitrosohydrazineca rboxamide. All six compounds showed a dose-dependent in vivo activity against leukaemias L1210 and P388. Compounds I and III were soluble in water.

Platinum (II) complexes of benzoic- and 3-methoxybenzoic acid hydrazides. Synthesis, characterization, and cytotoxic effect.

The complexes [Pt(bah)2X2], [Pt(NH3)(bah)Cl2].0.5H2O, [Pt(mbah)2X2], and [Pt(NH3)(mbah)Cl2] (bah = benzoic acid hydrazide, mbah = 3-methoxybenzoic acid hydrazide; X = Cl, Br, I) have been prepared and characterized by elemental analysis, electric conductivity, IR, 1H NMR, and electronic spectra.

Genotoxic and cytotoxic effects of 4-aroyl-1-nitrosohydrazine-carboxamides on O6-alkylguanine-DNA alkyltransferase-positive and -negative human cell lines.

Five different representatives (I-V) of a new class of bifunctional alkylating agents, the 4-aroyl-1-nitrosohydrazinecarboxamides ("nitrososemicarbazides"), were evaluated for their potential interaction with DNA and for their cytotoxic activity in vitro to O6-alkylguanine-DNA alkyltransferase-positive (Mer+) and -negative (Mer-) human cell lines. The HeLa MR cell line (Mer-) showed up to 20-fold higher sensitivity at IC50 (dose that inhibits colony formation by 50%) to agents I-V than did the HeLa S3 cell line (Mer+) in a colony-formation assay. These data were compared to those obtained by treatment of the two cell lines with carmustine, a currently used antitumor drug.