Please use this identifier to cite or link to this item:
http://hdl.handle.net/10397/89326
DC Field | Value | Language |
---|---|---|
dc.contributor | Department of Applied Biology and Chemical Technology | en_US |
dc.creator | Ye, J | en_US |
dc.creator | Chu, AJ | en_US |
dc.creator | Harper, R | en_US |
dc.creator | Chan, ST | en_US |
dc.creator | Shek, TL | en_US |
dc.creator | Zhang, Y | en_US |
dc.creator | Ip, M | en_US |
dc.creator | Sambir, M | en_US |
dc.creator | Artsimovitch, I | en_US |
dc.creator | Zuo, Z | en_US |
dc.creator | Yang, X | en_US |
dc.creator | Ma, C | en_US |
dc.date.accessioned | 2021-03-12T09:35:59Z | - |
dc.date.available | 2021-03-12T09:35:59Z | - |
dc.identifier.issn | 0022-2623 | en_US |
dc.identifier.uri | http://hdl.handle.net/10397/89326 | - |
dc.language.iso | en | en_US |
dc.publisher | American Chemical Society | en_US |
dc.rights | © 2020 American Chemical Society | en US |
dc.rights | This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Medicinal Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://dx.doi.org/10.1021/acs.jmedchem.0c00520. | en US |
dc.rights | Journal of Medicinal Chemistry is available at https://pubs.acs.org/journal/jmcmar. | en US |
dc.title | Discovery of antibacterials that inhibit bacterial RNA polymerase interactions with sigma factors | en_US |
dc.type | Journal/Magazine Article | en_US |
dc.identifier.spage | 7695 | en_US |
dc.identifier.epage | 7720 | en_US |
dc.identifier.volume | 63 | en_US |
dc.identifier.issue | 14 | en_US |
dc.identifier.doi | 10.1021/acs.jmedchem.0c00520 | en_US |
dcterms.abstract | 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. | en_US |
dcterms.accessRights | open access | en_US |
dcterms.bibliographicCitation | Journal of medicinal chemistry, 23 July 2020, v. 63, no. 14, p. 7695-7720 | en_US |
dcterms.isPartOf | Journal of medicinal chemistry | en_US |
dcterms.issued | 2020-07-23 | - |
dc.identifier.scopus | 2-s2.0-85088010039 | - |
dc.identifier.eissn | 1520-4804 | en_US |
dc.description.validate | 202103 bcvc | en_US |
dc.description.oa | Accepted Manuscript | en_US |
dc.identifier.FolderNumber | a0615-n02 | - |
dc.identifier.SubFormID | 601 | - |
dc.description.fundingSource | RGC | en_US |
dc.description.fundingSource | Others | en_US |
dc.description.fundingText | RGC: 25100017, 15100019, C5008-19G||Others: P0009742, P0030472, P000016 | en_US |
dc.description.pubStatus | Published | en_US |
dc.description.oaCategory | Green (AAM) | en_US |
Appears in Collections: | Journal/Magazine Article |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
a0615-n02.pdf | Pre-Published version | 3.27 MB | Adobe PDF | View/Open |
Page views
126
Last Week
0
0
Last month
Citations as of Apr 14, 2025
Downloads
286
Citations as of Apr 14, 2025
SCOPUSTM
Citations
21
Citations as of May 8, 2025
WEB OF SCIENCETM
Citations
20
Citations as of Oct 10, 2024

Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.