Synthesis of imidazoline and imidazo[2,1-c][1,2,4]triazole aryl derivatives containing the methylthio group as possible antibacterial agents
Bioorg Med Chem. 2006 Jun 1;14(11):3635-42. Epub 2006 Feb 7
Sztanke K, Pasternak K, Sidor-Wójtowicz A, Truchlińska J, Jóźwiak K
1-Arylimidazolidine-2-thiones (1a-g) were synthesized by the condensation reaction of N-arylethylenediamines with carbon disulfide in xylene medium. Their further alkylation with methyl iodide led to the formation of some biologically active 1-aryl-2-methylthio-imidazolines (2a-g). The 7-(4-methylphenyl)-3-methylthio-5H-6,7-dihydroimidazo[2,1-c][1,2,4]triazole (4b) was obtained by the alkylation of the respective 7-(4-methylphenyl)-2,5,6,7-tetrahydroimidazo[2,1-c][1,2,4]triazol-3(H)-thione (3b) with methyl iodide. Antimicrobial activities of 1-aryl-2-methylthio-imidazolines (2a-g) and the 7-(4-methylphenyl)-3- methylthio-5H-6,7-dihydroimidazo[2,1-c][1,2,4]triazole (4b) are presented. All tested compounds showed MIC in the range of 11.0-89.2 microM. Compounds 2a,e were found to be equipotent to chloramphenicol in vitro, whereas 2a,c,e-g and 4b showed superior activity (MIC) to ampicillin.
Linear patterns of Alzheimer's disease mutations along alpha-helices of presenilins as a tool for PS-1 model construction
J Neurochem. 2006 Sep;98(5):1560-72
Jozwiak K, Zekanowski C, Filipek S
We performed an analysis of mutation patterns in all 10 hydrophobic regions (HRs) of presenilin-1 (PS-1) and PS-2 using a recent database of Alzheimer's disease (AD) mutations. The linear patterns were confirmed and extended to areas spanning as many as three faces of a given HR. The complementary areas of residues free of AD mutations were identified based on the location of non-pathogenic polymorphisms and PS-1 versus PS-2 amino acid discordances. Taking into account the location of areas of AD mutations and mutation-free areas/regions, we proposed a preliminary model of PS-1 structure using a general stick-out-mutation rule. To build a molecular structure of PS-1 and preserve features of the preliminary model, we used bacteriorhodopsin template in homology/comparative modelling. Two molecular models were built differing in the location of C-terminal fragment helices. The models properly distinguish residues belonging to AD-affected sites and non-pathogenic areas, and may be used for classification purposes. They also comply with experimental results, such as differences in accessibility of the catalytic residues in uncleaved PS-1, and binding of PEN-2 by the PS-1 NF motif.
Non-competitive inhibitory activities of morphinan and morphine derivatives at the alpha 3 beta 4 Neuronal nicotinic acetylcholine receptor determined using nonlinear chromatography and chemometric techniques
Pharm Res. 2006 Sep;23(9):2175-82. Epub 2006 Aug 9
Jozwiak K, Moaddel R, Yamaguchi R, Maciuk A, Wainer IW