{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:45:58Z","timestamp":1792500358781,"version":"4.5.0"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T00:00:00Z","timestamp":1728604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Tuberculosis remains a serious global health threat, exacerbated by the rise of resistant strains. This study investigates the potential of two benzofuroxan (<jats:italic>Bfx<\/jats:italic>) derivatives, 5n and 5b, as targeted treatments for MDR-TB using <jats:italic>in silico<\/jats:italic>, <jats:italic>in vitro<\/jats:italic>, and <jats:italic>in vivo<\/jats:italic> methodologies. <jats:italic>In vitro<\/jats:italic> analyses showed that <jats:italic>Bfx<\/jats:italic> compounds have significant activity against <jats:italic>Mtb<\/jats:italic> H37Rv, with <jats:italic>Bfx<\/jats:italic> 5n standing out with a MIC<jats:sub>90<\/jats:sub> of 0.09\u2009\u00b1\u20090.04\u2009\u03bcM. Additionally, their efficacy against MDR and pre-XDR strains was superior compared to commercial drugs. These <jats:italic>Bfx<\/jats:italic> compounds have a narrow spectrum for mycobacteria, which helps avoid dysbiosis of the gut microbiota, and they also exhibit high selectivity and low toxicity. Synergism studies indicate that <jats:italic>Bfx<\/jats:italic> derivatives could be combined with rifampicin to enhance treatment efficacy and reduce its duration. Scanning electron microscopy revealed severe damage to the morphology of <jats:italic>Mtb<\/jats:italic> following treatment with <jats:italic>Bfx<\/jats:italic> 5n, showing significant distortions in the bacillary structures. Whole-genome sequencing of the 5n-resistant isolate suggests resistance mechanisms mediated by the Rv1855c gene, supported by <jats:italic>in silico<\/jats:italic> studies. <jats:italic>In vivo<\/jats:italic> studies showed that the 5n compound reduced the pulmonary load by 3.0 log<jats:sub>10<\/jats:sub> CFU\/mL, demonstrating superiority over rifampicin, which achieved a reduction of 1.23 log<jats:sub>10<\/jats:sub> CFU\/mL. In conclusion, <jats:italic>Bfx<\/jats:italic> derivatives, especially 5n, effectively address resistant infections caused by <jats:italic>Mtb<\/jats:italic>, suggesting they could be a solid foundation for future therapeutic developments against MDR-TB.<\/jats:p>","DOI":"10.3389\/fmicb.2024.1487829","type":"journal-article","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T04:42:04Z","timestamp":1728621724000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Screening of novel narrow-spectrum benzofuroxan derivatives for the treatment of multidrug-resistant tuberculosis through in silico, in vitro, and in vivo approaches"],"prefix":"10.3389","volume":"15","author":[{"given":"D\u00e9bora Leite","family":"Campos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian Shleider Carnero","family":"Canales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda Manaia","family":"Demarqui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme F. 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