Synthesis and biological activity of novel mono-indole and mono-benzofuran inhibitors of bacterial transcription initiation complex formation
Yükleniyor...
Dosyalar
Tarih
2015
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Pergamon-Elsevier Science Ltd
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
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 sigma(70)/sigma(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-sigma(70)/sigma(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. (C) 2015 Elsevier Ltd. All rights reserved.
Açıklama
Anahtar Kelimeler
Mono-indoles, Mono-benzofurans, RNA polymerase, sigma(70)/sigma(A) factors, Antibacterial activity, Structure-activity relationship (SAR), Rna-Polymerase Holoenzyme, Antibiotic-Resistance, Crystal-Structure, Sigma(70) Subunit, In-Vitro, Challenge, Discovery, Crisis, Impact, Drugs
Kaynak
Bioorganic & Medicinal Chemistry
WoS Q Değeri
Q2
Scopus Q Değeri
Q2
Cilt
23
Sayı
8
