180859-27-2Relevant academic research and scientific papers
Synthesis and biological activity of novel mono-indole and mono-benzofuran inhibitors of bacterial transcription initiation complex formation
Mielczarek, Marcin,Thomas, Ruth V.,Ma, Cong,Kandemir, Hakan,Yang, Xiao,Bhadbhade, Mohan,Black, David Stc.,Griffith, Renate,Lewis, Peter J.,Kumar, Naresh
, p. 1763 - 1775 (2015/03/30)
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.
Synthesis and biological activity of novel bis-indole inhibitors of bacterial transcription initiation complex formation
Mielczarek, Marcins,Devakaram, Ruth V.,Ma, Cong,Yang, Xiao,Kandemir, Hakan,Purwono, Bambang,Black, David Stc.,Griffith, Renate,Lewis, Peter J.,Kumar, Naresh
, p. 2882 - 2894 (2014/05/06)
The increasing resistance of bacteria against clinically approved antibiotics is resulting in an alarming decrease in therapeutic options for today's clinicians. We have targeted the essential interaction between bacterial RNA polymerase and σ70/σA for the development of lead molecules exhibiting a novel mechanism of antibacterial activity. Several classes of structurally related bis-indole inhibitors of bacterial transcription initiation complex formation were synthesized and their antimicrobial activities were evaluated. Condensation of indole-7- and indole-2-carbohydrazides with 7- and 2-trichloroacetylindoles or indole-7- and indole-2-glyoxyloyl chlorides resulted in the successful synthesis of 7,7′-, 2,2′-, 2,7′- and 3,2′-linked bis-indole derivatives with -CO-NH-NH-CO- and -CO-CO-NH-NH-CO- linkers. Indole-7-glyoxyloyl chlorides were reacted with hydrazine hydrate in different ratios to afford respective -CO-CO-NH-NH-CO-CO- bis-indole or hydrazide derivatives. The resulting compounds were found to be active against the β′-CH- σ70/σA2.2 interaction in ELISA assays and inhibited the growth of both Gram-positive and Gram-negative bacteria. Structure-activity relationship (SAR) studies were performed in order to identify the structural features of the synthesized inhibitors required for biological activity. This journal is the Partner Organisations 2014.
Reaction of some 4,6-dimethoxyindoles with oxalyl chloride
Black, David St.C.,Kumar, Naresh,McConnell, Darryl B.
, p. 8925 - 8936 (2007/10/03)
3-(4'-Chlorophenyl)-4,6-dimethoxyindole 1 undergoes reaction with oxalyl chloride to give the corresponding 2- and 7-glyoxyloyl chloride derivatives in differing proportions depending on the solvent and reaction temperature. The glyoxyloyl chlorides 2 and 3 were converted into the related glyoxylic acids, and also a wide range of glyoxylic esters and amides 4 and 5 respectively.
