title: Regulation of the Escherichia coli AtoSC two component system by synthetic biologically active 5;7;8-trimethyl-1;4-benzoxazine analogues.
abstract: The Escherichia coli AtoSC two component system;upon acetoacetate induction;regulates the expression of the atoDAEB operon;through His→Asp phopshotransfer;thus modulating important cellular processes. In this report the effect of seven 5,7,8-trimethyl-1,4-benzoxazine derivatives on the regulation of the E. coli AtoSC system was studied. The new compounds were tested for their effectiveness on the expression of the atoC and the regulated atoDAEB operon. The non-substituted 5,7,8-trimethyl-1,4-benzoxazine (4a), was the most potent inducer on atoC transcription;resulting in accumulation of AtoC protein. The induction of atoC by 4a was specific;since no effect was observed on the other genes of the system (atoS and atoDAEB). Moreover;compound 4a was shown to significantly up-regulate the in vitro kinase activity of the histidine kinase AtoS without altering the protein levels in the cell. Interestingly;this compound appeared to modulate the acetoacetate-mediated induction of the atoDAEB promoter by the AtoSC system. These data provide the first evidence for a differential modulator role of 5,7,8-trimethyl-1,4-benzoxazine;on the AtoSC two component system mediated signaling.
authors.affiliation: Laboratory of Biochemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
authors.forename: Panagiota S
authors.initials: PS
authors.lastname: Filippou
authors.forename: Eftychia N
authors.initials: EN
authors.lastname: Koini
authors.forename: Theodora
authors.initials: T
authors.lastname: Calogeropoulou
authors.forename: Panagiota
authors.initials: P
authors.lastname: Kalliakmani
authors.forename: Christos A
authors.initials: CA
authors.lastname: Panagiotidis
authors.forename: Dimitrios A
authors.initials: DA
authors.lastname: Kyriakidis
mesh_terms: D000090:Acetoacetates / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D048588:Benzoxazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D058990:Molecular Targeted Therapy; D009876:Operon / Q000187:drug effects; D011494:Protein Kinases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000090:Acetoacetates; D000900:Anti-Bacterial Agents; D048588:Benzoxazines; D029968:Escherichia coli Proteins; C016635:acetoacetic acid; D011494:Protein Kinases; C505586:AtoS protein, E coli