{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T09:34:10Z","timestamp":1787045650207,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Synthetic compounds, particularly thiadiazine derivatives with antibacterial properties, have emerged as promising candidates in addressing the growing challenge of bacterial multidrug resistance. Thiadiazine derivatives are six-membered heterocyclic compounds containing two nitrogen atoms and one sulfur atom, exhibiting diverse medical and pharmacological activities. This study aimed to evaluate the potentiating activity of thiadiazine derivatives against multidrug-resistant bacteria. Methods: ADMET (absorption, distribution, metabolism, excretion, and toxicity) assays were performed to assess similarity with more than 370,000 three-dimensional structures of bioactive compounds. The multidrug-resistant bacterial strains Staphylococcus aureus 10 and Pseudomonas aeruginosa 24 were used to investigate both the direct antibacterial activity and the antibiotic-modifying activity of thiadiazine derivatives. Results: The thiadiazine analogs did not exhibit direct antibacterial activity, presenting a minimum inhibitory concentration of 1024 \u03bcg\/mL. However, they demonstrated a significant antibiotic-modifying effect, potentiating the activity of conventional antibiotics, particularly norfloxacin, against the tested strains. In silico analyses indicated that the analogs predominantly exhibited affinity for G protein-coupled receptors and possessed physicochemical characteristics compatible with potential drug candidates. Conclusions: Although the evaluated thiadiazine derivatives lacked direct antibacterial activity, they significantly enhanced the efficacy of antibiotics against multidrug-resistant bacteria. Combined with their favourable in silico pharmacokinetic and physicochemical profiles, these findings suggest that thiadiazine derivatives may represent promising antibiotic adjuvants for combating multidrug-resistant bacterial infections.<\/jats:p>","DOI":"10.3390\/antibiotics15080794","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:01:26Z","timestamp":1786968086000},"page":"794","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Vitro and In Silico Evaluation of the Potentiating Effect of Thiadiazine Derivatives Against Multidrug-Resistant (MDR) Bacterial Strains"],"prefix":"10.3390","volume":"15","author":[{"given":"Evandro Gomes da Silva","family":"J\u00fanior","sequence":"first","affiliation":[{"name":"Laboratory of Microbiology and Molecular Biology (LMBM), Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7785-3186","authenticated-orcid":false,"given":"Ingrid Gon\u00e7alves Pereira","family":"Dantas","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Molecular Biology (LMBM), Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8123-517X","authenticated-orcid":false,"given":"Matheus dos Santos","family":"Louren\u00e7o","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Molecular Biology (LMBM), Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Arthur de Oliveira","family":"Borges","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Molecular Biology (LMBM), Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6544-0141","authenticated-orcid":false,"given":"Isaac Moura","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Molecular Biology (LMBM), Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7522-2989","authenticated-orcid":false,"given":"Jos\u00e9 Thy\u00e1lisson da Costa","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Molecular Biology (LMBM), Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Carolina Ferreira","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Molecular Biology (LMBM), Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla Ramos Freitas","family":"Alexandre","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Molecular Biology (LMBM), Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana\u00edna Esmeraldo","family":"Rocha","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Molecular Biology (LMBM), Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Karollyna do Nascimento Silva","family":"Leandro","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Molecular Biology (LMBM), Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2664-4336","authenticated-orcid":false,"given":"Igor Jos\u00e9 dos Santos","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry, Institute of Pharmaceutical Sciences, Federal University of Alagoas, Macei\u00f3 57072-900, AL, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3187-183X","authenticated-orcid":false,"given":"Jo\u00e3o Xavier de","family":"Ara\u00fajo-J\u00fanior","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry, Institute of Pharmaceutical Sciences, Federal University of Alagoas, Macei\u00f3 57072-900, AL, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1527-4501","authenticated-orcid":false,"given":"Edeildo Ferreira","family":"da Silva-J\u00fanior","sequence":"additional","affiliation":[{"name":"Biological and Molecular Chemistry Research Group, Institute of Chemistry and Biotechnology, Federal University of Alagoas, Macei\u00f3 57072-900, AL, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago Mendon\u00e7a","family":"de Aquino","sequence":"additional","affiliation":[{"name":"Laboratory of Synthesis and Research in Medicinal Chemistry, Research Group on Therapeutic Strategies\u2014GPET, Institute of Chemistry and Biotechnology, Federal University of Alagoas, Macei\u00f3 57072-900, AL, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3588-833X","authenticated-orcid":false,"given":"Francisco Jaime Bezerra Mendon\u00e7a","family":"Junior","sequence":"additional","affiliation":[{"name":"Laboratory of Synthesis and Drug Delivery-LSVM, Department of Biological Science, State University of Paraiba, Jo\u00e3o Pessoa 58071-160, PB, 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