{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T12:32:43Z","timestamp":1792758763847,"version":"4.5.0"},"reference-count":67,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Developing new antimicrobial drugs is crucial for combating global drug resistance caused by microbial infections. Here, a new series of pyrazole and isoxazole derivatives were synthesized using a multicomponent reaction based on ethylvanillin and active methylene group as well as binucleophile reagents under basic conditions. The designed derivatives were confirmed using FT\u2010IR,\n                    <jats:sup>1<\/jats:sup>\n                    H NMR,\n                    <jats:sup>13<\/jats:sup>\n                    C NMR, Mass spectrum, and elemental analysis. Subsequently, all the designed derivatives were evaluated against four bacterial and one fungal strain. The synthesized derivatives demonstrated significant to good antimicrobial activity with low MIC values against the tested strains, especially against\n                    <jats:italic>Bacillus subtilis<\/jats:italic>\n                    ,\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    , and\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    . Notably, four compounds\n                    <jats:bold>14<\/jats:bold>\n                    ,\n                    <jats:bold>17<\/jats:bold>\n                    ,\n                    <jats:bold>20<\/jats:bold>\n                    , and\n                    <jats:bold>24<\/jats:bold>\n                    showed promising MIC values ranging from 7.8 to 62.5\u2009\u00b5g\/mL) against gram\u2010positive strains and for gram\u2010negative strains (MIC\u2009=\u200931.25\u2013125\u2009\u00b5g\/mL), compared to gentamycin (15.62 and 31.25\u2009\u00b5g\/mL), respectively. In addition, these derivatives revealed MIC values from 15.62 to 31.25\u2009\u00b5g\/mL compared to fluconazole (MIC\u2009=\u200915.62\u2009\u00b5g\/mL) against\n                    <jats:italic>C. albicans<\/jats:italic>\n                    . Additionally, the structure activity relationships (SAR) were discussed. Moreover, the MBC and MFC values were evaluated and the results exhibited bactericidal and fungicidal properties, except for 5\u2010hydroxy\u20101\n                    <jats:italic>H<\/jats:italic>\n                    \u2010pyrazole\u20101\u2010carbothioamide derivative\n                    <jats:bold>14<\/jats:bold>\n                    that demonstrated bacteriostatic activity against\n                    <jats:italic>B. subtilis<\/jats:italic>\n                    . Moreover, the biofilm inhibitory activity of the most promising derivatives demonstrated a dose\u2010dependent effect and inhibit biofilm formation from 96.17\u2009\u00b1\u20090.004% to 66.04\u2009\u00b1\u20090.004%. Among these compounds, the 5\u2010hydroxy\u20101\n                    <jats:italic>H<\/jats:italic>\n                    \u2010pyrazole\u20101\u2010carbothioamide derivative\n                    <jats:bold>14<\/jats:bold>\n                    emerged as the most active, exhibiting a biofilm inhibitory percentage (BIP) of 96.17\u2009\u00b1\u20090.004% compared to gentamicin's BIP of 96.44\u2009\u00b1\u20090.004% at 75% MIC. Finally, a docking simulation of the most promising derivatives was conducted within the active site of Las R, suggesting a potential mode of action, where these derivatives displayed different binding interaction with low binding affinity. Moreover, in\u2010silico oral bioavailability and toxicity profile was predicted for the most promising derivatives and exhibited promising physicochemical properties with a safe toxicity profile, opening up the possibility of the discovery of new antibiotics.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70189","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T08:29:07Z","timestamp":1763368147000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Exploration Novel of Pyrazole and Isoxazole Derivatives as Potential Antimicrobial Agents: Design, Synthesis, Structure Activity Relationship Study, and Antibiofilm Activity With Molecular Docking Simulation"],"prefix":"10.1002","volume":"86","author":[{"given":"Khadija E.","family":"Saadon","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science (Girls) Al\u2010Azhar University Nasr City Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Ragab","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science (Boys) Al\u2010Azhar University Nasr City Cairo Egypt"},{"name":"Chemistry Department, Faculty of Science Galala University Galala City Suez Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia M. 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