{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:05:43Z","timestamp":1790229943231,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPQ)","award":["404927\/2023-8"],"award-info":[{"award-number":["404927\/2023-8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Motivated by the search for novel antimicrobials against opportunistic resistant pathogens and based on the reported antimicrobial activity of phthalimides, two series of phthalimide and N-phthaloylglycine esters were designed to investigate whether the addition of butyl and aryl groups enhances their antimicrobial properties. Thus, in vitro antimicrobial activity, antifungal mechanism of action, effect combined with Chloramphenicol, in silico\/vitro toxicity, and a docking molecular were studied. Phthalimide and N-phthaloylglycine aryl esters were obtained in yields of 75\u201398%. Phthalimide aryl ester 3b (R = Me) showed the best results against Gram-(+) and Gram-(\u2212) bacteria, S. aureus and P. aeruginosa, respectively, and yeast fungi, C. tropicalis and C. albicans, with MIC values equal to 128 \u00b5g\u00b7mL\u22121. Regarding the antifungal mechanism of action on C. albicans, the MIC values of compound 3b changed from 128 to 1024 \u00b5g\u00b7mL\u22121 in the presence of ergosterol. Furthermore, compound 3b showed synergy with Chloramphenicol against P. aeruginosa, with a FICI value equal to 0.5. Finally, the four most promising compounds had their in silico\/vitro toxicity evaluated, which showed moderate toxicity to non-toxicity on Artemia salina larvae. With the exception of Chloramphenicol, all selected compounds, including Fluconazole, are potentially hepatotoxic, but they were predicted not to cause skin sensitization, suggesting a potential application for topical use. Molecular docking revealed that compound 3b exhibits superior binding affinity and stability with the 50S ribosomal subunit (\u221292.69 kcal\u00b7mol\u22121) compared to Chloramphenicol, and a unique \u03c0\u2013sulfur interaction with CYP51, suggesting its potential as a dual-action antibacterial and antifungal candidate against resistant pathogens.<\/jats:p>","DOI":"10.3390\/life15040518","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T13:48:20Z","timestamp":1742824100000},"page":"518","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Antimicrobial Investigation of Phthalimide and N-Phthaloylglycine Esters: Activity, Mechanism of Action, Synergism and Ecotoxicity"],"prefix":"10.3390","volume":"15","author":[{"given":"Francinara S.","family":"Alves","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Bioenergia e S\u00edntese Org\u00e2nica (LPBS), Department of Chemistry, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abra\u00e3o P.","family":"Sousa","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Bioenergia e S\u00edntese Org\u00e2nica (LPBS), Department of Chemistry, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9205-5230","authenticated-orcid":false,"given":"Alexandre","family":"Almeida-J\u00fanior","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Bioenergia e S\u00edntese Org\u00e2nica (LPBS), Department of Chemistry, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscila S. V.","family":"Lima","sequence":"additional","affiliation":[{"name":"N\u00facleo de Qu\u00edmica de Heterociclos (NUQUIMHE), Department of Chemistry, Federal University of Santa Maria, Santa Maria 97105-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7558-9655","authenticated-orcid":false,"given":"Marcelo F. R.","family":"Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Multiusu\u00e1rio de Caracteriza\u00e7\u00e3o e An\u00e1lises (LMCA), Institute of Research in Drugs and Medicines, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 L. F. M.","family":"Galv\u00e3o","sequence":"additional","affiliation":[{"name":"Nova Esperan\u00e7a University Hospital, Nova Esperan\u00e7a College, Jo\u00e3o Pessoa 58067-695, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edeltrudes O.","family":"Lima","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1708-4066","authenticated-orcid":false,"given":"Helivaldo D. S.","family":"Souza","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Bioenergia e S\u00edntese Org\u00e2nica (LPBS), Department of Chemistry, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3103-5604","authenticated-orcid":false,"given":"Jos\u00e9 A. S.","family":"Luis","sequence":"additional","affiliation":[{"name":"Center of Education and Health, Federal University of Campina Grande, Cuit\u00e9 58429-600, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr\u00f4nio F.","family":"Athayde-Filho","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Bioenergia e S\u00edntese Org\u00e2nica (LPBS), Department of Chemistry, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8156-2272","authenticated-orcid":false,"given":"Gabriela F.","family":"Fiss","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Bioenergia e S\u00edntese Org\u00e2nica (LPBS), Department of Chemistry, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"ref_1","unstructured":"(2025, January 02). 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