{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:24:14Z","timestamp":1791397454107,"version":"4.3.3"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["R21AI105867, R03AI153454, U54AI057159"],"award-info":[{"award-number":["R21AI105867, R03AI153454, U54AI057159"]}]},{"DOI":"10.13039\/100011138","name":"AgBioResearch, Michigan State University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100011138","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2023,9,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Nitro-containing compounds have emerged as important agents in the control of tuberculosis (TB). From a whole-cell high-throughput screen for\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (Mtb) growth inhibitors, 10 nitro-containing compounds were prioritized for characterization and mechanism of action studies. HC2209, HC2210, and HC2211 are nitrofuran-based prodrugs that need the cofactor F\n                    <jats:sub>420<\/jats:sub>\n                    machinery for activation. Unlike pretomanid which depends only on deazaflavin-dependent nitroreductase (Ddn), these nitrofurans depend on Ddn and possibly another F\n                    <jats:sub>420<\/jats:sub>\n                    -dependent reductase for activation. These nitrofurans also differ from pretomanid in their potent activity against\n                    <jats:italic>Mycobacterium abscessus<\/jats:italic>\n                    . Four dinitrobenzamides (HC2217, HC2226, HC2238, and HC2239) and a nitrofuran (HC2250) are proposed to be inhibitors of decaprenyl-phosphoryl-ribose 2\u2032-epimerase 1 (DprE1), based on isolation of resistant mutations in\n                    <jats:italic>dprE1<\/jats:italic>\n                    . Unlike other DprE1 inhibitors, HC2250 was found to be potent against non-replicating persistent bacteria, suggesting additional targets. Two of the compounds, HC2233 and HC2234, were found to have potent, sterilizing activity against replicating and non-replicating Mtb\n                    <jats:italic>in vitro<\/jats:italic>\n                    , but a proposed mechanism of action could not be defined. In a pilot\n                    <jats:italic>in vivo<\/jats:italic>\n                    efficacy study, HC2210 was orally bioavailable and efficacious in reducing bacterial load by ~1 log in a chronic murine TB infection model.\n                  <\/jats:p>","DOI":"10.1128\/aac.00474-23","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T09:03:26Z","timestamp":1692781406000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Discovery and characterization of antimycobacterial nitro-containing compounds with distinct mechanisms of action and\n                    <i>in vivo<\/i>\n                    efficacy"],"prefix":"10.1128","volume":"67","author":[{"given":"Ifeanyichukwu E.","family":"Eke","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Michigan State University , East Lansing, Michigan, 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