N-(1,3,4-Oxadiazol-2-yl)Benzamides as Antibacterial Agents against Neisseria gonorrhoeae

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dc.contributor.authorNaclerio, George A.en
dc.contributor.authorAbutaleb, Nader S.en
dc.contributor.authorAlhashimi, Marwaen
dc.contributor.authorSeleem, Mohamed N.en
dc.contributor.authorSintim, Herman O.en
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.date.accessioned2021-04-29T17:09:17Zen
dc.date.available2021-04-29T17:09:17Zen
dc.date.issued2021-03en
dc.description.abstractThe Centers for Disease Control and Prevention (CDC) recognizes Neisseria gonorrhoeae as an urgent-threat Gram-negative bacterial pathogen. Additionally, resistance to frontline treatment (dual therapy with azithromycin and ceftriaxone) has led to the emergence of multidrug-resistant N. gonorrhoeae, which has caused a global health crisis. The drug pipeline for N. gonorrhoeae has been severely lacking as new antibacterial agents have not been approved by the FDA in the last twenty years. Thus, there is a need for new chemical entities active against drug-resistant N. gonorrhoeae. Trifluoromethylsulfonyl (SO2CF3), trifluoromethylthio (SCF3), and pentafluorosulfanyl (SF5) containing N-(1,3,4-oxadiazol-2-yl)benzamides are novel compounds with potent activities against Gram-positive bacterial pathogens. Here, we report the discovery of new N-(1,3,4-oxadiazol-2-yl)benzamides (HSGN-237 and -238) with highly potent activity against N. gonorrhoeae. Additionally, these new compounds were shown to have activity against clinically important Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and Listeria monocytogenes (minimum inhibitory concentrations (MICs) as low as 0.25 mu g/mL). Both compounds were highly tolerable to human cell lines. Moreover, HSGN-238 showed an outstanding ability to permeate across the gastrointestinal tract, indicating it would have a high systemic absorption if used as an anti-gonococcal therapeutic.en
dc.description.notesThis research was funded by Purdue University and the National Institute of Allergy And Infectious Diseases of the National Institutes of Health under Award Number T32AI148103.en
dc.description.sponsorshipPurdue University; National Institute of Allergy And Infectious Diseases of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [T32AI148103]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3390/ijms22052427en
dc.identifier.eissn1422-0067en
dc.identifier.issue5en
dc.identifier.other2427en
dc.identifier.pmid33671065en
dc.identifier.urihttp://hdl.handle.net/10919/103169en
dc.identifier.volume22en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectNeisseria gonorrhoeaeen
dc.subject1,3,4-oxadiazoleen
dc.subjectantibioticen
dc.subjectantimicrobial resistanceen
dc.titleN-(1,3,4-Oxadiazol-2-yl)Benzamides as Antibacterial Agents against Neisseria gonorrhoeaeen
dc.title.serialInternational Journal of Molecular Sciencesen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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Scholarly Works, Biomedical Sciences and Pathobiology
Destination Area: Global Systems Science (GSS)