Isoquinoline Antimicrobial Agent: Activity against Intracellular Bacteria and Effect on Global Bacterial Proteome

dc.contributor.authorKaranja, Caroline W.en
dc.contributor.authorNaganna, Nimishettien
dc.contributor.authorAbutaleb, Nader S.en
dc.contributor.authorDayal, Neetuen
dc.contributor.authorOnyedibe, Kenneth I.en
dc.contributor.authorAryal, Umaen
dc.contributor.authorSeleem, Mohamed N.en
dc.contributor.authorSintim, Herman O.en
dc.date.accessioned2022-08-11T13:52:09Zen
dc.date.available2022-08-11T13:52:09Zen
dc.date.issued2022-08-10en
dc.date.updated2022-08-11T11:50:04Zen
dc.description.abstractA new class of alkynyl isoquinoline antibacterial compounds, synthesized via Sonogashira coupling, with strong bactericidal activity against a plethora of Gram-positive bacteria including methicillin- and vancomycin-resistant <i>Staphylococcus aureus (S. aureus)</i> strains is presented. HSN584 and HSN739, representative compounds in this class, reduce methicillin-resistant <i>S. aureus</i> (MRSA) load in macrophages, whilst vancomycin, a drug of choice for MRSA infections, was unable to clear intracellular MRSA. Additionally, both HSN584 and HSN739 exhibited a low propensity to develop resistance. We utilized comparative global proteomics and macromolecule biosynthesis assays to gain insight into the alkynyl isoquinoline mechanism of action. Our preliminary data show that HSN584 perturb <i>S. aureus</i> cell wall and nucleic acid biosynthesis. The alkynyl isoquinoline moiety is a new scaffold for the development of potent antibacterial agents against fatal multidrug-resistant Gram-positive bacteria.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationKaranja, C.W.; Naganna, N.; Abutaleb, N.S.; Dayal, N.; Onyedibe, K.I.; Aryal, U.; Seleem, M.N.; Sintim, H.O. Isoquinoline Antimicrobial Agent: Activity against Intracellular Bacteria and Effect on Global Bacterial Proteome. Molecules 2022, 27, 5085.en
dc.identifier.doihttps://doi.org/10.3390/molecules27165085en
dc.identifier.urihttp://hdl.handle.net/10919/111512en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectantimicrobial resistanceen
dc.subjectallkynyl isoquinoliesen
dc.subjectSonogashira couplingen
dc.subjectintracellular clearanceen
dc.titleIsoquinoline Antimicrobial Agent: Activity against Intracellular Bacteria and Effect on Global Bacterial Proteomeen
dc.title.serialMoleculesen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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