Radioprotective activity and toxicity of copolymer 2-methyl-5-vinyl pyridine with 2-methyl-5-vinylpyridinium-n-oxide

In experiments in mice, hamsters and dogs therapeutic radioprotective efficiency and toxicity of new water-soluble copolymer were studied. It was found that at intramuscular injection of the copolymer to dogs in a dose of 5 mg/kg 24 h after irradiation with a dose of 3.30 Gy (LD85/45) it showed pronounced therapeutic effect (68.1%). In mice and hamsters, the effect was less pronounced: 42-21% after irradiation with a dose of 8.0 Gy. The copolymer is low toxic substance and according to the State standards of Russian Federation belongs to the fourth class (harmless).     

Effect of co-polymer 2-methyl-5-vinylpyridine and 2-methyl-5- vinylpyridinium-n-oxide radiation induced myelodepression in mice

On the model of cytopenia induced in mice by irradiation with a dose of 4.0 Gy it was shown that injection of examined copolymer (400 mg/kg) 3 h after irradiation exerts positive effect on haemopoietic system: the decrease of damage and acceleration of repair processes.     

Synthesis and cholinergic affinity of diastereomeric and enantiomeric isomers of 1-methyl-2-(2-methyl-1,3-dioxolan-4-yl)- pyrrolidine, 1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine and of Their iodomethylates

Four out of the eight possible stereoisomers of 1-methyl-2-(2-methyl-1,3-dioxolan-4-yl)pyrrolidine, 1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine and the corresponding iodomethylates have been synthesised. They were formally derived from hybridisation of potent though unselective agonists studied before, such as 1,3-dioxolane 1 and 1,3-oxathiolane 2, with the structure of nicotine. It was expected that, by exalting the molecular complexity of the parent compounds, in particular through stereochemical complication in the proximity of the critical cationic head of the molecule, the chance to find agonists able to discriminate among cholinergic receptors subtypes would increase. The relative and absolute configuration of the compounds obtained has been established by means of NMR spectroscopy and X-ray crystallography. In preliminary studies, their binding affinity has been evaluated on rat brain nicotinic and muscarinic receptors. While none of the compounds showed any nicotinic affinity up to the dose of 10 microM, most of the iodomethylates were endowed with promising affinity for the muscarinic receptors.     

Production of 2-methyl-1-butanol and 3-methyl-1-butanol in engineered Corynebacterium glutamicum

The pentanol isomers 2-methyl-1-butanol and 3-methyl-1-butanol represent commercially interesting alcohols due to their potential application as biofuels. For a sustainable microbial production of these compounds, Corynebacterium glutamicum was engineered for producing 2-methyl-1-butanol and 3-methyl-1-butanol via the Ehrlich pathway from 2-keto-3-methylvalerate and 2-ketoisocaproate, respectively. In addition to an already available 2-ketoisocaproate producer, a 2-keto-3-methylvalerate accumulating C. glutamicum strain was also constructed. For this purpose, we reduced the activity of the branched-chain amino acid transaminase in an available C. glutamicum l-isoleucine producer (K2P55) via a start codon exchange in the ilvE gene enabling accumulation of up to 3.67 g/l 2-keto-3-methylvalerate. Subsequently, nine strains expressing different gene combinations for three 2-keto acid decarboxylases and three alcohol dehydrogenases were constructed and characterized. The best strains accumulated 0.37 g/l 2-methyl-1-butanol and 2.76 g/l 3-methyl-1-butanol in defined medium within 48 h under oxygen deprivation conditions, making these strains ideal candidates for additional strain and process optimization.     

Synthesis of 5-Alkyl-5-methyl-2-hydroxy-2-cyclopentenones

A hydrogen bacterium strain, N34, and its oxygen-resistant segregant strain, Y38, were subjected to a taxonomical study. Since both strains were capable of N₂-fixation, N₂-fixing facultative hydrogen autotrophs listed in “Bergey’s Manual of Systematic Bacteriology” were used for comparison. Both strains produced a water-insoluble carotenoid pigment, zeaxanthin dirhamnoside, indicating that both should be classified into the genus Xanthobacter. Then, the differential characteristics of the two species of the genus Xanthobacter, X. autotrophicus and X. flavus, were investigated as to both strains. The vitamin requirement, the sensitivity to oxygen under autotrophic conditions, the inducibility of hydrogenase, the substrate range of carbohydrates and N₂-fixing growth characteristics of both strains were almost completely opposite to those of X. flavus. Moreover, both strains coincided exactly with X. autotrophicus in morphological and other physiological characteristics. From these results both strains were identified as Xanthobacter autotrophicus.     

2,3-Dimethoxy-5-methyl-1,4-benzoquinones and 2-methyl-1,4-naphthoquinones: glycation inhibitors with lipid peroxidation activity

Anti-glycation activity of our anti-oxidant quinone library was measured and several 2,3-dimethoxy-5-methyl-1,4-benzoquinones and 2-methyl-1,4-naphthoquinones were identified as novel inhibitors of glycation, of which 2,3-dimethoxy-5-methyl-1,4-benzoquinones 13b is the most potent glycation inhibitor with around 50 microM of the IC(50) value.     

A simple preparation of 2-methyl-5alpha-cholest-2-ene

A convenient preparation of 2-methyl-5α-cholest-2-ene from 5α-cholestan-3β-ol is described.     

Reactions of d-glucose,d-xylose,and d-erythrose with 2-methyl-2-propanethiol

The reaction of d-glucose and d-xylose with 2-methyl-2-propanethiol in conc. hydrochloric acid yielded tert-butyl 1-thioglycopyranosides (products of kinetic and thermodynamic control). Di-tert-butyl dithioacetals (12–14) were obtained from the acetylated aldehydo-derivatives of d-glucose, d-xylose, and d-erythrose. On brief treatment with conc. hydrochloric acid, 12 and 13 gave tert-butyl 1-thio-α- and -β-glycopyranosides and 14 gave the corresponding furanosides.     

Identification of 2-methyl-3-hydroxydecanoic and 2-methyl-3-hydroxytetradecanoic acids in the 'lipid X' fraction of the Bordetella pertussis endotoxin.

The 'lipid X' fraction, released from the Bordetella pertussis endotoxin upon treatment with trifluoroacetic acid of pH 3 at 50 degrees C, was shown to contain, in addition to 3-hydroxydecanoic, 3-hydroxydodecanoic, 3-hydroxytetradecanoic, and tetradec-2-enoic acids, 2-methyl-3-hydroxydecanoic-, and 2-methyl-3-hydroxytetradecanoic acids. The structure of these was established by gas-liquid chromatography/mass spectrometry.     

Synthesis and antitumor activity of 1-substituted-2-methyl-5-nitrobenzimidazoles

Different substituents were introduced in position 1 of 2-methyl-5(6)-nitro-1H-benzimidazole (2) in order to obtain different side chains having different heterocyclic compounds, for example, thiadiazoles (5-7), tetrazoles (8, 9a, b), triazoles (11-13), thiazoles (14a-e), triazines (10, 16, 17), and imidazoles (18a-c). The antitumor effect of compounds 1, 2, 2a, 4, 5, 7, 8, 9a, 10, 13, 14a, 15, 16, and 18c was studied against breast cancer (MCF7) and compounds 2 [IC(50)=4.52 microg] and 7 [IC(50)=8.29 microg] were found to be active.     

Microbial transformation of 2-amino-4-methyl-3-nitropyridine

Biotransformation of the highly substituted pyridine derivative 2-amino-4-methyl-3-nitropyridine by Cunninghamella elegans ATCC 26269 yielded three products each with a molecular weight of 169?Da which were identified as 2-amino-5-hydroxy-4-methyl-3-nitropyridine, 2-amino-4-hydroxymethyl-3-nitropyridine, and 2-amino-4-methyl-3-nitropyridine-1-oxide. Biotransformation by Streptomyces antibioticus ATCC 14890 gave two different products each with a molecular weight of 169?Da; one was acid labile and converted to the other stable product under acidic conditions. The structure of the stable product was established as 2-amino-4-methyl-3-nitro-6(1H)-pyridinone, and that of the less stable product was assigned as its tautomer 2-amino-6-hydroxy-4-methyl-3-nitropyridine. Four of the five biotransformation products are new compounds. Several strains of Aspergillus also converted the same substrate to the lactam 2-amino-4-methyl-3-nitro-6(1H)-pyridinone. Microbial hydroxylation by C. elegans was found to be inhibited by sulfate ion. In order to improve the yield and productivity of the 5-hydroxylation reaction by C. elegans, critical process parameters were determined and Design of Experiments (DOE) analyses were performed. Biotransformation by C. elegans was scaled up to 15-l fermentors providing 2-amino-5-hydroxy-4-methyl-3-nitropyridine at ca. 13?% yield in multi-gram levels. A simple isolation process not requiring chromatography was developed to provide purified 2-amino-5-hydroxy-4-methyl-3-nitropyridine of excellent quality.     

Synthesis and spectroscopic characterization of site-specific 2-amino-1-methyl-6-phenylimidazo

The aim of the present study is to determine the chemical structure and conformation of DNA adducts formed by incubation of the bioactive form of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), N-acetoxy-PhIP, with a single-stranded 11mer oligodeoxyribonucleotide. Using conditions optimized to give the C8-dG-PhIP adduct as the major product, sufficient material was synthesized for NMR solution structure determination. The NMR data indicate that in duplex DNA this adduct exists in equilibrium between two different conformational states. In the main conformer, the covalently bound PhIP molecule intercalates in the helix, whilst in the minor conformation the PhIP ligand is probably solvent exposed. In addition to the C8-dG-PhIP adduct, at least eight polar adducts are found after reaction of N-acetoxy-PhIP with the oligonucleotide. Three of these were purified for further characterization and shown to exhibit lowest energy UV absorption bands in the range 342–347 nm, confirming the presence of PhIP or PhIP derivative. Accurate mass determination of two of the polar adducts by negative ion MALDI-TOF MS revealed ions consistent with a spirobisguanidino-PhIP derivative and a ring-opened adduct. The third adduct, which has the same mass as the C8-dG-PhIP oligonucleotide adduct, may contain PhIP bound to the N² position of guanine.     

Biodegradation of Acetochlor and 2-methyl-6-ethylaniline by Bacillus subtilis and Pseudomonasfluorescens

Microbiology - Two bacterial strains, Pseudomonas fluorescens KT3 and Bacillus subtilis 2M6E, isolated from soil utilized acetochlor and 2-methyl-6-ethylaniline (2M6E) as carbon and nitrogen...