DC FieldValueLanguage
dc.contributorChinese Mainland Affairs Office-
dc.contributorDepartment of Applied Biology and Chemical Technology-
dc.creatorQiu, Y-
dc.creatorChan, ST-
dc.creatorLin, L-
dc.creatorShek, TL-
dc.creatorTsang, TF-
dc.creatorBarua, N-
dc.creatorZhang, Y-
dc.creatorIp, M-
dc.creatorChan, PKS-
dc.creatorBlanchard, N-
dc.creatorHanquet, G-
dc.creatorZuo, Z-
dc.creatorYang, X-
dc.creatorMa, C-
dc.date.accessioned2021-05-13T08:32:56Z-
dc.date.available2021-05-13T08:32:56Z-
dc.identifier.issn0223-5234-
dc.identifier.urihttp://hdl.handle.net/10397/89947-
dc.language.isoenen_US
dc.publisherElsevier Massonen_US
dc.subjectAntimicrobial activityen_US
dc.subjectDiarylamineen_US
dc.subjectDiarylimineen_US
dc.subjectInhibitoren_US
dc.subjectMethicillin-resistant Staphylococcus aureusen_US
dc.subjectProtein-protein interactionen_US
dc.titleDesign, synthesis and biological evaluation of antimicrobial diarylimine and –amine compounds targeting the interaction between the bacterial NusB and NusE proteinsen_US
dc.typeJournal/Magazine Articleen_US
dc.identifier.spage214-
dc.identifier.epage231-
dc.identifier.volume178-
dc.identifier.doi10.1016/j.ejmech.2019.05.090-
dcterms.abstractDiscovery of antimicrobial agents with a novel model of action is in urgent need for the clinical management of multidrug-resistant bacterial infections. Recently, we reported the identification of a first-in-class bacterial ribosomal RNA synthesis inhibitor, which interrupted the interaction between the bacterial transcription factor NusB and NusE. In this study, a series of diaryl derivatives were rationally designed and synthesized based on the previously established pharmacophore model. Inhibitory activity against the NusB-NusE binding, circular dichroism of compound treated NusB, antimicrobial activity, cytotoxicity, hemolytic property and cell permeability using Caco-2 cells were measured. Structure-activity relationship and quantitative structure–activity relationship were also concluded and discussed. Some of the derivatives demonstrated improved antimicrobial activity than the hit compound against a panel of clinically important pathogens, lowering the minimum inhibition concentration to 1–2 μg/mL against Staphylococcus aureus, including clinical strains of methicillin-resistant Staphylococcus aureus at a level comparable to some of the marketed antibiotics. Given the improved antimicrobial activity, specific inhibition of target protein-protein interaction and promising pharmacokinetic properties without significant cytotoxicity, this series of diaryl compounds have high potentials and deserve for further studies towards a new class of antimicrobial agents in the future.-
dcterms.accessRightsembargoed access-
dcterms.bibliographicCitationEuropean journal of medicinal chemistry, 15 Sept. 2019, v. 178, p. 214-231-
dcterms.isPartOfEuropean journal of medicinal chemistry-
dcterms.issued2019-09-15-
dc.identifier.scopus2-s2.0-85066948832-
dc.identifier.pmid31185412-
dc.identifier.eissn1768-3254-
dc.description.validate202105 bcvc-
dc.description.oaNot applicable-
dc.identifier.FolderNumbera0734-n04-
dc.identifier.SubFormID1303-
dc.description.fundingSourceRGC-
dc.description.fundingSourceOthers-
dc.description.fundingTextRGC: 25100017-
dc.description.fundingTextOthers: P0020297, P0000161-
dc.description.pubStatusPublished-
dc.date.embargo2021.09.30en_US
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