{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T16:21:15Z","timestamp":1771950075842,"version":"3.50.1"},"reference-count":60,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T00:00:00Z","timestamp":1554854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006668","name":"Fondo para la Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT 2014\u20100959"],"award-info":[{"award-number":["PICT 2014\u20100959"]}],"id":[{"id":"10.13039\/501100006668","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:p><jats:italic>Brucella<\/jats:italic> spp. are pathogenic intracellular Gram\u2010negative bacteria adapted to life within cells of several mammals, including humans. These bacteria are the causative agent of brucellosis, one of the zoonotic infections with the highest incidence in the world and for which a human vaccine is still unavailable. Current therapeutic treatments against brucellosis are based on the combination of two or more antibiotics for prolonged periods, which may lead to antibiotic resistance in the population. Riboflavin (vitamin B2) is biosynthesized by microorganisms and plants but mammals, including humans, must obtain it from dietary sources. Owing to the absence of the riboflavin biosynthetic enzymes in animals, this pathway is nowadays regarded as a rich resource of targets for the development of new antimicrobial agents. In this work, we describe a high\u2010throughput screening approach to identify inhibitors of the enzymatic activity of riboflavin synthase, the last enzyme in this pathway. We also provide evidence for their subsequent validation as potential drug candidates in an <jats:italic>in\u00a0vitro<\/jats:italic> brucellosis infection model. From an initial set of 44\u00a0000 highly diverse low molecular weight compounds with drug\u2010like properties, we were able to identify ten molecules with 50% inhibitory concentrations in the low micromolar range. Further <jats:italic>Brucella<\/jats:italic> culture and intramacrophagic replication experiments showed that the most effective bactericidal compounds share a 2\u2010Phenylamidazo[2,1\u2010b][1,3]benzothiazole chemical scaffold. Altogether, these findings set up the basis for the subsequent lead optimization process and represent a promising advancement in the pursuit of novel and effective antimicrobial compounds against brucellosis.<\/jats:p>","DOI":"10.1111\/febs.14829","type":"journal-article","created":{"date-parts":[[2019,3,30]],"date-time":"2019-03-30T14:54:50Z","timestamp":1553957690000},"page":"2522-2535","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["A high\u2010throughput screening for inhibitors of riboflavin synthase identifies novel antimicrobial compounds to treat brucellosis"],"prefix":"10.1111","volume":"286","author":[{"given":"Mar\u00eda In\u00e9s","family":"Serer","sequence":"first","affiliation":[{"name":"Fundaci\u00f3n Instituto Leloir IIBBA\u2010CONICET Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariela del 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