Synthesis and biological activity of novel mono-indole and mono-benzofuran inhibitors of bacterial transcription initiation complex formation

Bioorganic & Medicinal Chemistry
Marcin MielczarekNaresh Kumar

Abstract

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 σ(70)/σ(A) 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-σ(70)/σ(A) 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.

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Citations

Mar 5, 2016·Journal of Research in Medical Sciences : the Official Journal of Isfahan University of Medical Sciences·Ghadamali KhodarahmiElham Khodarahmi
Jan 15, 2016·Microbiology and Molecular Biology Reviews : MMBR·Cong MaPeter J Lewis
Sep 29, 2019·Expert Opinion on Therapeutic Patents·Kamal M Dawood
Aug 18, 2021·Transcription·Michael MillerPeter J Lewis
Aug 31, 2021·RSC Chemical Biology·Rashi KahanAnna Barnard

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