- Title
- Synthesis and biological activity of novel mono-indole and mono-benzofuran inhibitors of bacterial transcription initiation complex formation
- Creator
- Mielczarek, Marcin; Thomas, Ruth V.; Ma, Cong; Kandemir, Hakan; Yang, Xiao; Bhadbhade, Mohan; Black, David StC.; Griffith, Renate; Lewis, Peter J.; Kumar, Naresh
- Relation
- NHMRC.1008014 http://purl.org/au-research/grants/nhmrc/1008014
- Relation
- Bioorganic and Medicinal Chemistry Vol. 23, Issue 8, p. 1763-1775
- Publisher Link
- http://dx.doi.org/10.1016/j.bmc.2015.02.037
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2015
- Description
- Our ongoing research focused on targeting transcription initiation in bacteria has resulted in synthesis of several classes of mono-indole and mono-benzofuran inhibitors that targeted the essential protein-protein interaction between RNA polymerase core and σ70/σA factors in bacteria. In this study, the reaction of indole-2-, indole-3-, indole-7- and benzofuran-2-glyoxyloyl chlorides with amines and hydrazines afforded a variety of glyoxyloylamides and glyoxyloylhydrazides. Similarly, condensation of 2- and 7-trichloroacetylindoles with amines and hydrazines delivered amides and hydrazides. The novel molecules were found to inhibit the RNA polymerase-σ70/σA interaction as measured by ELISA, and also inhibited the growth of both Gram-positive and Gram-negative bacteria in culture. Structure-activity relationship (SAR) studies of the mono-indole and mono-benzofuran inhibitors suggested that the hydrophilic-hydrophobic balance is an important determinant of biological activity.
- Subject
- mono-indoles; mono-benzofurans; RNA polymerase; σ<sup>70</sup>/σ<sup>A</sup>factors; antibacterial activity; structure–activity relationship (SAR)
- Identifier
- http://hdl.handle.net/1959.13/1336780
- Identifier
- uon:27697
- Identifier
- ISSN:0968-0896
- Language
- eng
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