Show simple item record

dc.contributor.authorMegahed, Sarah H
dc.contributor.authorRasheed, Sari
dc.contributor.authorHerrmann, Jennifer
dc.contributor.authorEl-Hossary, Ebaa M
dc.contributor.authorEl-Shabrawy, Yahia I
dc.contributor.authorAbadi, Ashraf H
dc.contributor.authorEngel, Matthias
dc.contributor.authorMüller, Rolf
dc.contributor.authorAbdel-Halim, Mohammad
dc.contributor.authorHamed, Mostafa M
dc.date.accessioned2022-02-17T17:57:49Z
dc.date.available2022-02-17T17:57:49Z
dc.date.issued2022-01-07
dc.identifier.citationBioorg Med Chem Lett. 2022 Mar 1;59:128531. doi: 10.1016/j.bmcl.2022.128531. Epub 2022 Jan 7.en_US
dc.identifier.pmid35007723
dc.identifier.doi10.1016/j.bmcl.2022.128531
dc.identifier.urihttp://hdl.handle.net/10033/623169
dc.description.abstractBacterial resistance to currently used antibiotics demands the development of novel antibacterial agents with good safety margins and sufficient efficacy against multi-drug resistant isolates. We have previously described the synthesis of N-butyl-2-(butylthio)quinazolin-4-amine (I) as an optimized hit with broad-spectrum antibacterial activity and low cytotoxicity. In addition, we have identified a potential growing vector for this series of compounds. Herein, we describe further hit optimization which includes systematic diversifications of both the benzenoid part and the substituents at position 6 and 7 of compound I. Growing of the molecule beside the core modifications yielded several compounds with remarkable anti(myco)bacterial activity against a panel of pathogenic bacteria, including drug-resistant strains. Compound 12 showed a 2-4 fold improvement in activity than I against S. aureus Newman, S. pneumoniae DSM-20566 and E. faecalis DSM-20478. The compounds also showed a good safety profile towards human HepG2 cells.en_US
dc.language.isoenen_US
dc.publisherElsevier Ltd.en_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectAntibacterialen_US
dc.subjectCytotoxicityen_US
dc.subjectPyrazolo[3,4-d]pyrimidineen_US
dc.subjectQuinazolineen_US
dc.subjectThieno[2,3-d]pyrimidineen_US
dc.titleNovel 2,4-disubstituted quinazoline analogs as antibacterial agents with improved cytotoxicity profile: Modification of the benzenoid part.en_US
dc.typeArticleen_US
dc.identifier.eissn1464-3405
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalBioorganic & medicinal chemistry lettersen_US
dc.source.volume59
dc.source.beginpage128531
dc.source.endpage
refterms.dateFOA2022-02-17T17:57:49Z
dc.source.journaltitleBioorganic & medicinal chemistry letters
dc.source.countryEngland


Files in this item

Thumbnail
Name:
Publisher version
Thumbnail
Name:
Megahed et al.pdf
Size:
621.9Kb
Format:
PDF
Description:
accepted manuscript
Thumbnail
Name:
Megahed_graph_abstract.jpg
Size:
25.09Kb
Format:
JPEG image
Description:
graphical abstract
Thumbnail
Name:
Final SI_Megahed.pdf
Size:
657.2Kb
Format:
PDF
Description:
supporting information

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International