{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T21:56:16Z","timestamp":1790546176473,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Antimicrobial resistance (AMR) has severely compromised the clinical utility of classical sulfonamide antibiotics, primarily owing to the emergence of resistance\u2010associated dihydropteroate synthase variants. In this study, sixteen N\u2010(1H\u2010indazolyl) aryl sulfonamide hybrids were evaluated as potential DHPS inhibitors against\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    and\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    using disk diffusion, broth microdilution (MIC\n                    <jats:sub>80<\/jats:sub>\n                    ), and minimum bactericidal concentration (MBC) assays. Active compounds were characterized by in silico ADME and toxicity profiling, with molecular docking performed against wild\u2010type DHPS and the sulfonamide\u2010resistant Sul1 variant. Antibacterial activity was species\u2010dependent: compound 4 showed the strongest activity against\n                    <jats:italic>E. coli<\/jats:italic>\n                    (MIC\u00a0=\u00a032\u00a0\u00b5g\/mL), while compounds 11 and 16 were most potent against\n                    <jats:italic>S. aureus<\/jats:italic>\n                    (MIC\u00a0=\u00a032\u00a0\u00b5g\/mL), outperforming sulfathiazole and sulfisoxazole. All hybrids showed superior docking affinities to sulfamethoxazole (SMX), with compound 11 showing the highest affinity for wild\u2010type DHPS (\u22127.79\u00a0kcal\/mol); compound 4 retained favorable binding against Sul1 (\u22126.83\u00a0kcal\/mol), suggesting potential resistance resilience. Structure\u2013activity analysis showed antibacterial efficacy is governed by aryl sulfonyl electronic effects, steric balance at the C7 indazole position, and physicochemical properties affecting Gram\u2010negative membrane permeability. These findings support indazole\u2013sulfonamide hybrids as promising scaffolds that may retain predicted binding complementarity toward the Sul1\u2010resistant DHPS variant, warranting validation against resistant isolates and purified DHPS enzymes.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.71656","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:25:49Z","timestamp":1788521149000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["N\u2010(1H\u2010Indazolyl) Aryl Sulfonamide Hybrids as Potential Dihydropteroate Synthase Inhibitors: In Vitro Antibacterial Activity Against\n                    <i>Escherichia coli<\/i>\n                    and\n                    <i>Staphylococcus aureus<\/i>\n                    and Computational Modeling"],"prefix":"10.1002","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6582-2857","authenticated-orcid":false,"given":"Romaisaa","family":"Boudza","sequence":"first","affiliation":[{"name":"Euromed University of Fes, UEMF  Morocco"},{"name":"Department of Microbiology and Ecology. Faculty of Biology Universitat De Val\u00e8ncia  Burjassot Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdaous","family":"Elandaloussi","sequence":"additional","affiliation":[{"name":"Euromed University of Fes, UEMF  Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5112-0049","authenticated-orcid":false,"given":"Khalid","family":"Boujdi","sequence":"additional","affiliation":[{"name":"Faculty of Sciences and Techniques of Tangier  Tangier Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9138-5465","authenticated-orcid":false,"given":"Jaume","family":"Segura\u2010Garcia","sequence":"additional","affiliation":[{"name":"Department of Computer Science, School of Engineering Universitat De Val\u00e8ncia  Burjassot Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1967-2758","authenticated-orcid":false,"given":"Nabil El","family":"Brahmi","sequence":"additional","affiliation":[{"name":"Euromed University of Fes, UEMF  Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5021-3571","authenticated-orcid":false,"given":"Sa\u00efd El","family":"Kazzouli","sequence":"additional","affiliation":[{"name":"Euromed University of Fes, UEMF  Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6557-4430","authenticated-orcid":false,"given":"Isma\u00efl","family":"Moukadiri","sequence":"additional","affiliation":[{"name":"Euromed University of Fes, UEMF  Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4360-611X","authenticated-orcid":false,"given":"Sergi","family":"Maicas","sequence":"additional","affiliation":[{"name":"Euromed University of Fes, UEMF  Morocco"},{"name":"Department of Microbiology and Ecology. 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