{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T12:15:05Z","timestamp":1771071305949,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    New series of 2\u2010imino\/oxo\u2010tetrahydropyrimidines (\n                    <jats:bold>4a\u20104j<\/jats:bold>\n                    ), and fused pyrimidines (\n                    <jats:bold>5a\u20105i<\/jats:bold>\n                    and\n                    <jats:bold>6a\u20106h<\/jats:bold>\n                    ) were designed and synthesized as attractive scaffolds to be investigated in vitro and in vivo for antimicrobial activity against gram\u2010positive\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    , gram\u2010negative\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    and\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    , and fungus\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    . In the in vitro antimicrobial screening using agar diffusion method, compounds\n                    <jats:bold>4\u2009d, 4\u2009f, 6a<\/jats:bold>\n                    and\n                    <jats:bold>6\u2009d<\/jats:bold>\n                    showed broad\u2010spectrum antimicrobial activity against all the tested strains when compared to levofloxacin as a reference drug. Moreover, compound\n                    <jats:bold>4\u2009f<\/jats:bold>\n                    showed higher antibacterial activity against all the tested microorganisms with MIC\u2009=\u200922\u201345\u2009\u00b5M compared with levofloxacin with MIC\u2009=\u200950\u2010\u2009&gt;\u2009708\u2009\u00b5M. Compound\n                    <jats:bold>5\u2009g<\/jats:bold>\n                    exhibited lower IC\n                    <jats:sub>50<\/jats:sub>\n                    than that of reference trimethoprim (TMP) towards the DHFR enzyme inhibition. Additionally, compounds\n                    <jats:bold>4\u2009d, 4\u2009f, 4\u2009g, 6\u2009d<\/jats:bold>\n                    and\n                    <jats:bold>6\u2009f<\/jats:bold>\n                    had kept the superiority over the reference drug with IC\n                    <jats:sub>50<\/jats:sub>\n                    ranging from 4.10 to 4.77\u2009\u00b5M. Compounds\n                    <jats:bold>4\u2009f<\/jats:bold>\n                    and\n                    <jats:bold>6a<\/jats:bold>\n                    were subjected to in vivo evaluation for their antibacterial activity. They caused a significant reduction in abscess volume and area in the skin of mice inoculated with\n                    <jats:italic>S. aureus<\/jats:italic>\n                    . Moreover, compound\n                    <jats:bold>4\u2009f<\/jats:bold>\n                    had reduced the immune\u2010expression of interleukin\u20101\u03b2 in the isolated tissues of the infected skin. Molecular docking results were in a good agreement with the DHFR enzyme assay results and justified the binding profiles and affinities profile of all tested compounds. Conclusively, compounds\n                    <jats:bold>4\u2009d, 4\u2009f, 5\u2009g, 6a<\/jats:bold>\n                    and\n                    <jats:bold>6\u2009d<\/jats:bold>\n                    are very promising candidates for further antimicrobial studies.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70163","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T14:55:45Z","timestamp":1758639345000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring Novel Tetrahydropyrimidine and Fused Pyrimidine\u2010Based Compounds as DHFR Inhibitors and Antimicrobial Agents: Synthesis, In Vitro, In Vivo, and In Silico Studies"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6998-8711","authenticated-orcid":false,"given":"Menna M.","family":"Sherif","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Delta University for Science and Technology Gamasa Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basem","family":"Mansour","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Delta University for Science and Technology Gamasa Egypt"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy University of Kut Kut Iraq"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"May A.","family":"El\u2010Antrawy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Biotechnology, Faculty of Pharmacy Delta University for Science and Technology Gamasa Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heba A.","family":"Abdelaziz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Biochemistry, Faculty of Pharmacy Delta University for Science and Technology Gamasa Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sahar M. 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