{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:21:28Z","timestamp":1790803288126,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A series of new quinazolin-2,4-dione derivatives incorporating amide\/eight-membered nitrogen-heterocycles 2a\u2013c, in addition, acylthiourea\/amide\/dithiolan-4-one and\/or phenylthiazolidin-4-one 3a\u2013d and 4a\u2013d. The starting compound 1 was prepared by reaction of 4-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-benzoyl chloride with ammonium thiocyanate and cyanoacetic acid hydrazide. The reaction of 1 with strong electrophiles, namely, o-aminophenol, o-amino thiophenol, and\/or o-phenylene diamine, resulted in corresponding quinazolin-2,4-dione derivatives incorporating eight-membered nitrogen-heterocycles 2a\u2013d. Compounds 3a\u2013d and 4a\u2013d were synthesized in good-to-excellent yield through a one-pot multi-component reaction (MCR) of 1 with carbon disulfide and\/or phenyl isocyanate under mild alkaline conditions, followed by ethyl chloroacetate, ethyl iodide, methyl iodide, and\/or concentrated HCl, respectively. The obtained products were physicochemically characterized by melting points, elemental analysis, and spectroscopic techniques, such as FT-IR, 1H-NMR, 13C-NMR, and MS. The antibacterial efficacy of the obtained eleven molecules was examined in vitro against two Gram-positive bacterial strains (Staphylococcus aureus and Staphylococcus\u00a0haemolyticus). Furthermore, Computer-Aided Drug Design (CADD) was performed on the synthesized derivatives, standard drug (Methotrexate), and reported antibacterial drug with the target enzymes of bacterial strains (S. aureus and S. haemolyticus) to explain their binding mode of actions. Notably, our findings highlight compounds 2b and 2c as showing both the best antibacterial activity and docking scores against the targets. Finally, according to ADMET predictions, compounds 2b and 2c possessed acceptable pharmacokinetics properties and drug-likeness properties.<\/jats:p>","DOI":"10.3390\/molecules29235529","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T10:17:23Z","timestamp":1732270643000},"page":"5529","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of Quinazolin-2,4-Dione Derivatives as Promising Antibacterial Agents: Synthesis, In Vitro, In Silico ADMET and Molecular Docking Approaches"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4616-0224","authenticated-orcid":false,"given":"Aboubakr H.","family":"Abdelmonsef","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science, South Valley University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8799-0235","authenticated-orcid":false,"given":"Mohamed","family":"El-Naggar","sequence":"additional","affiliation":[{"name":"Pure and Applied Chemistry Group, Chemistry Department, College of Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4679-8615","authenticated-orcid":false,"given":"Amal O. A.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, South Valley University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2886-1294","authenticated-orcid":false,"given":"Asmaa S.","family":"Abdelgeliel","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, Faculty of Science, South Valley University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihsan A.","family":"Shehadi","sequence":"additional","affiliation":[{"name":"Pure and Applied Chemistry Group, Chemistry Department, College of Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Mosallam","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, South Valley University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Khodairy","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Sohag University, Sohag 82524, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s00214-023-03052-2","article-title":"DFT Study of the Condensation Products of 2-Chloro-3-Formylquinolines with o-Aminophenol, o-Aminothiophenol and o-Phenylenediamine","volume":"142","author":"Benabila","year":"2023","journal-title":"Theor. 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