Antibacterial activities and DNA-cleavage properties of novel fluorescent imidazo-phenanthroline derivatives.

Design and biological activities of fluorescent imidazo-phenanthroline derivatives; (E)-5-((4-((4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenoxy)methyl)benzylidene)amino)- isophthalicacid, 2 and 2-(4-(((5-chloroquinolin-8-yl)oxy)methyl)phenyl)-1H-imidazo[4,5f] [1,10]phenanthroline, 3, have been reported. Their characterizations were performed by spectroscopic techniques. Their promising photophysical behaviours were observed in absorbance and fluorescence studies. The antibacterial activities of the compounds were determined against seven different microorganisms; Bacillus subtilis ATCC 6633(G + ), Pseudomonas aeruginosa ATCC 29853(G-), Escherichia coli ATCC 35,218 (G-), Enterococcus faecalis ATCC 292,112 (G + ), Salmonella typhimurium ST-10 (G-), Streptococcus mutans NCTC 10,449 (G + ), and Staphylococcus aureus ATCC 25923(G + ). MIC values of 3 was determined as 156,25 µM on all tested bacteria. A preliminary study of the structure-activity relationship (SAR) also revealed that the antimicrobial activity depended on the substituents on the phenyl ring. The electron withdrawing Cl-substitued compound 3 most favour for antimicrobial activity even at lowest concentration compared to other compounds. DNA-cleavage activities of the compounds were also investigated. The interactions of the compounds with supercoiled pBR322 plasmid DNA were obtained by agarose gel electrophoresis. All imidazo-phenanthroline derivatives were found to be highly effective on DNA, even at the lowest concentrations because of their planar nature which provides ease of bind to the helix structure of DNA.

A Genome-Wide Screen for Wortmannin-Resistant Mutants in Schizosaccharomyces pombe: The Phosphorylation-Impaired Mutants Are Resistant to Signaling Defect.

Complex human diseases such as metabolic disorders, cancer, neurodegenerative diseases, and mitochondrial dysfunctions arise from the biochemical or genetic defects in various cellular processes. Therefore, it is important to understand which metabolic processes are affected by which cellular impairment. Because genome-wide screening of mutant collections (haploid/diploid deletion library) provides important clues for the understanding of conserved biological processes and for finding potential target genes, we screened the haploid mutant collection of Schizosaccharomyces pombe with wortmannin that inhibits phosphatidylinositol-3-kinase signaling. Using genome-wide screening, we determined that 52 mutants were resistant to this chemical. When 52 genes that are deleted in these mutants were grouped in 41 different biological processes, we found that 37 of them have human orthologues and 4 genes were associated with human metabolic disorders. In addition, when we examined the pathways in which these 52 genes function, we determined that 9 genes were related to phosphorylation process. These results might provide new insights for better understanding of certain human diseases.