Furanyl-rhodanines are unattractive drug candidates for development as inhibitors of bacterial RNA polymerase.
Previous studies suggest that furanyl-rhodanines might specifically inhibit bacterial RNA polymerase (RNAP). We further explored three compounds from this class. Although they inhibited RNAP, each compound also inhibited malate dehydrogenase and chymotrypsin. Using biosensors responsive to inhibition of macromolecular synthesis and membrane damaging assays, we concluded that in bacteria, one compound inhibited DNA synthesis and another caused membrane damage. The third rhodanine lacked antibacterial activity. We consider furanyl-rhodanines to be unattractive RNAP inhibitor drug candidates.
Mariner
Katherine R
KR
Antimicrobial Research Centre and Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom.
Trowbridge
Rachel
R
Agarwal
Anil K
AK
Miller
Keith
K
O'Neill
Alex J
AJ
Fishwick
Colin W G
CW
Chopra
Ian
I
D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D002462:Cell Membrane / Q000187:drug effects; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000494:pharmacology*; D008291:Malate Dehydrogenase / Q000037:antagonists & inhibitors; D012236:Rhodanine / Q000009:adverse effects* / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D012236:Rhodanine; D008291:Malate Dehydrogenase; D012321:DNA-Directed RNA Polymerases; D002918:Chymotrypsin