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

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.