Novel 2,4-disubstituted quinazoline analogs as antibacterial agents with improved cytotoxicity profile: Modification of the benzenoid part.
dc.contributor.author | Megahed, Sarah H | |
dc.contributor.author | Rasheed, Sari | |
dc.contributor.author | Herrmann, Jennifer | |
dc.contributor.author | El-Hossary, Ebaa M | |
dc.contributor.author | El-Shabrawy, Yahia I | |
dc.contributor.author | Abadi, Ashraf H | |
dc.contributor.author | Engel, Matthias | |
dc.contributor.author | Müller, Rolf | |
dc.contributor.author | Abdel-Halim, Mohammad | |
dc.contributor.author | Hamed, Mostafa M | |
dc.date.accessioned | 2022-02-17T17:57:49Z | |
dc.date.available | 2022-02-17T17:57:49Z | |
dc.date.issued | 2022-01-07 | |
dc.identifier.citation | Bioorg Med Chem Lett. 2022 Mar 1;59:128531. doi: 10.1016/j.bmcl.2022.128531. Epub 2022 Jan 7. | en_US |
dc.identifier.pmid | 35007723 | |
dc.identifier.doi | 10.1016/j.bmcl.2022.128531 | |
dc.identifier.uri | http://hdl.handle.net/10033/623169 | |
dc.description.abstract | Bacterial 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.iso | en | en_US |
dc.publisher | Elsevier Ltd. | en_US |
dc.rights | Attribution 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Antibacterial | en_US |
dc.subject | Cytotoxicity | en_US |
dc.subject | Pyrazolo[3,4-d]pyrimidine | en_US |
dc.subject | Quinazoline | en_US |
dc.subject | Thieno[2,3-d]pyrimidine | en_US |
dc.title | Novel 2,4-disubstituted quinazoline analogs as antibacterial agents with improved cytotoxicity profile: Modification of the benzenoid part. | en_US |
dc.type | Article | en_US |
dc.identifier.eissn | 1464-3405 | |
dc.contributor.department | HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. | en_US |
dc.identifier.journal | Bioorganic & medicinal chemistry letters | en_US |
dc.source.volume | 59 | |
dc.source.beginpage | 128531 | |
dc.source.endpage | ||
refterms.dateFOA | 2022-02-17T17:57:49Z | |
dc.source.journaltitle | Bioorganic & medicinal chemistry letters | |
dc.source.country | England |