From indole to pyrrole, furan, thiophene and pyridine: Search for novel small molecule inhibitors of bacterial transcription initiation complex formation.

Autor: Thach O; School of Chemistry, UNSW Australia, Sydney, NSW 2052, Australia., Mielczarek M; School of Chemistry, UNSW Australia, Sydney, NSW 2052, Australia., Ma C; School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia., Kutty SK; School of Chemistry, UNSW Australia, Sydney, NSW 2052, Australia., Yang X; School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia., Black DS; School of Chemistry, UNSW Australia, Sydney, NSW 2052, Australia., Griffith R; School of Medical Sciences, UNSW Australia, Sydney, NSW 2052, Australia., Lewis PJ; School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia., Kumar N; School of Chemistry, UNSW Australia, Sydney, NSW 2052, Australia. Electronic address: n.kumar@unsw.edu.au.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2016 Mar 15; Vol. 24 (6), pp. 1171-82. Date of Electronic Publication: 2016 Jan 21.
DOI: 10.1016/j.bmc.2016.01.040
Abstrakt: The search for small molecules capable of inhibiting transcription initiation in bacteria has resulted in the synthesis of N,N'-disubstituted hydrazines and imine-carbohydrazides comprised of indole, pyridine, pyrrole, furan and thiophene using the respective trichloroacetyl derivatives, carbohydrazides and aldehydes. Replacement of the indole moiety by smaller heterocycles linked by CONHNC linkers afforded a broad variety of compounds efficiently targeting the RNA polymerase-σ(70)/σ(A) interaction as determined by ELISA and exhibiting increased inhibition of the growth of Escherichia coli compared to Bacillus subtilis in culture. The structural features of the synthesized transcription initiation inhibitors needed for antibacterial activity were identified employing molecular modelling and structure-activity relationship (SAR) studies.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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