20643-68-9Relevant academic research and scientific papers
Discovery of Antibacterials That Inhibit Bacterial RNA Polymerase Interactions with Sigma Factors
Ye, Jiqing,Chu, Adrian Jun,Harper, Rachel,Chan, Shu Ting,Shek, Tsun Lam,Zhang, Yufeng,Ip, Margaret,Sambir, Mariya,Artsimovitch, Irina,Zuo, Zhong,Yang, Xiao,Ma, Cong
, p. 7695 - 7720 (2020)
Formation of a bacterial RNA polymerase (RNAP) holoenzyme by a catalytic core RNAP and a sigma (σ) initiation factor is essential for bacterial viability. As the primary binding site for the housekeeping σ factors, the RNAP clamp helix domain represents an attractive target for novel antimicrobial agent discovery. Previously, we designed a pharmacophore model based on the essential amino acids of the clamp helix, such as R278, R281, and I291 (Escherichia coli numbering), and identified hit compounds with antimicrobial activity that interfered with the core-σ interactions. In this work, we rationally designed and synthesized a class of triaryl derivatives of one hit compound and succeeded in drastically improving the antimicrobial activity against Streptococcus pneumoniae, with the minimum inhibitory concentration reduced from 256 to 1 μg/mL. Additional characterization of antimicrobial activity, inhibition of transcription, in vitro pharmacological properties, and cytotoxicity of the optimized compounds demonstrated their potential for further development.
First-in-class inhibitors targeting the interaction between bacterial RNA polymerase and sigma initiation factor affect the viability and toxin release of streptococcus pneumoniae
Ye, Jiqing,Chu, Adrian Jun,Lin, Lin,Yang, Xiao,Ma, Cong
, (2019)
Novel antimicrobial classes are in desperate need for clinical management of infections caused by increasingly prevalent multi-drug resistant pathogens. The protein-protein interaction between bacterial RNA polymerase (RNAP) and the housekeeping sigma ini
COMPOUNDS WITH ANTIMICROBIAL ACTIVITY
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Paragraph 0170-0172, (2020/01/24)
Provided herein are compounds useful in the treatment of bacterial infections, pharmaceuticals comprising the same, and methods of use and preparation thereof.
Small molecule inhibitors of PARP activity
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Page/Page column 20, (2011/05/05)
Componds and pharmaceutical compositions are provided that inhibit the activity of poly ADP-ribose synthetase (PARP). Such componds are useful in the treatment of various diseases, conditions and injuries such as stroke, myocardial infarction, ischemia-pe
