Diarylpropane-1,3-dione derivatives as TetR-inducing tetracycline mimetics: Synthesis and biological investigations

C. Kormann, I. Pimenta, S. Lober, C. Wimmer, H. Lanig, Tim Clark, W. Hillen, P. Gmeiner

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)2924-2933
Number of pages10
JournalChemBioChem
Volume10
Issue number18
DOIs
Publication statusPublished - 2009

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