ABSTRACT
A bacterial strain 5HP capable of degrading and utilizing 5-hydroxypicolinic acid as the sole source of carbon and energy was isolated from soil. In addition, the isolate 5HP could also utilize 3-hydroxypyridine and 3-cyanopyridine as well as nicotinic, benzoic and p-hydroxybenzoic acids for growth in the basic salt media. On the basis of 16S rRNA gene sequence analysis, the isolate 5HP was shown to belong to the genus Pusillimonas. Both the bioconversion analysis using resting cells and the enzymatic assay showed that the degradation of 5-hydroxypicolinic acid, 3-hydroxypyridine and nicotinic acid was inducible and proceeded via formation of the same metabolite, 2,5-dihydroxypyridine. The activity of a novel enzyme, 5-hydroxypicolinate 2-monooxygenase, was detected in the cell-free extracts prepared from 5-hydroxypicolinate-grown cells. The enzyme was partially purified and was shown to catalyze the oxidative decarboxylation of 5-hydroxypicolinate to 2,5-dihydroxypyridine. The activity of 5-hydroxypicolinate 2-monooxygenase was dependent on O2, NADH and FAD.
Subject(s)
Bacterial Proteins/metabolism , Betaproteobacteria/enzymology , Mixed Function Oxygenases/metabolism , Picolinic Acids/metabolism , RNA, Ribosomal, 16S/genetics , Soil Microbiology , Bacterial Proteins/isolation & purification , Benzoic Acid/metabolism , Betaproteobacteria/classification , Betaproteobacteria/genetics , Betaproteobacteria/isolation & purification , Biodegradation, Environmental , Flavin-Adenine Dinucleotide/metabolism , Mixed Function Oxygenases/isolation & purification , NAD/metabolism , Niacin/metabolism , Oxygen/metabolism , Parabens/metabolism , Phylogeny , Pyridines/metabolism , RNA, Ribosomal, 16S/classification , Sequence Analysis, DNAABSTRACT
2,3-Dihydro-1H-1,5-benzodiazepine amidines were prepared by nucleophilic substitution of 2,3,4,5-tetrahydro-1H-1,5-benzodiazepine-2-thiones. Evaluation of the 13 synthesised amidines as antitumour agents was carried out in vitro against 60 human tumour cell lines at the National Cancer Institute, Bethesda, USA. The screening revealed a moderate cell growth inhibition of two derivatives on all cell lines at concentrations ranging from 10(-5) to 10(-4) mol/l. Log P values were theoretically calculated. The more active derivatives were found to exhibit a higher lipophilicity.
