title: Diarylpropane-1,3-dione derivatives as TetR-inducing tetracycline mimetics: Synthesis and biological investigations.
abstract: Synthesis, biological investigations and molecular docking studies of nonantibiotic and nontetracyclic inducers that feature a minimal key motif of the natural lead tetracycline are presented. The diarylpropane-1,3-dione motif was identified as the minimal substructure responsible for TetR induction by tetracyclines. The first nontetracyclic surrogates of the natural tetracyclines displayed significant inducing effects for TetR(BD)S135L, whereby the chlorohydroxyphenyl-substituted beta-diketone 31 displayed the highest activity. Interestingly, antibiotic activity could not be detected for 31. Homology modeling based on the X-ray structure of 7-chlorotetracycline bound to TetR indicated analogous binding modes for the natural inducer and the synthetic diarylpropane-1,3-dione derivatives.
authors.affiliation: Department of Chemistry and Pharmacy, Emil Fischer Center, Friedrich Alexander University, Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kormann
authors.forename: Irina
authors.initials: I
authors.lastname: Pimenta
authors.forename: Stefan
authors.initials: S
authors.lastname: Löber
authors.forename: Cornelius
authors.initials: C
authors.lastname: Wimmer
authors.forename: Harald
authors.initials: H
authors.lastname: Lanig
authors.forename: Timothy
authors.initials: T
authors.lastname: Clark
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hillen
authors.forename: Peter
authors.initials: P
authors.lastname: Gmeiner
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D047188:Chalcones / Q000737:chemistry*; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D008968:Molecular Conformation; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013754:Tetracyclines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D047188:Chalcones; D012097:Repressor Proteins; D013754:Tetracyclines; C034811:tetracycline resistance-encoding transposon repressor protein