Small molecule inhibitors of bacterial transcription complex formation

Knoevenagel condensation was employed to generate a set of molecules potentially capable of inhibiting the RNA polymerase-sigma(70)/sigma(A) interaction in bacteria. Synthesis was achieved via reactions between a variety of indole-7-carbaldehydes and rhodanine, N-allylrhodanine, barbituric acid or thiobarbituric acid. A library of structurally diverse compounds was examined by enzyme-linked immunosorbent assay (ELISA) to assess the inhibition of the targeted protein-protein interaction. Inhibition of bacterial growth was also evaluated using Bacillus subtilis and Escherichia coli cultures. The structure-activity relationship studies demonstrated the significance of particular structural features of the synthesized molecules for RNA polymerase-sigma(70)/sigma(A) interaction inhibition and antibacterial activity. Docking was investigated as an in silico method for the further development of the compounds. (C) 2017 Elsevier Ltd. All rights reserved.