{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T13:25:00Z","timestamp":1771421100437,"version":"3.50.1"},"reference-count":94,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["21-64-00017p"],"award-info":[{"award-number":["21-64-00017p"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Russian Ministry of Science and Higher Education","award":["121031300056-8"],"award-info":[{"award-number":["121031300056-8"]}]},{"name":"Russian Ministry of Science and Higher Education","award":["FWUE-2025-0006"],"award-info":[{"award-number":["FWUE-2025-0006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tuberculosis (TB) remains a global health issue exacerbated by spreading drug resistance and lengthy treatment regimens. Targeting bacterial DNA-repair pathways, particularly those counteracting host-generated genotoxic stress, represents a promising strategy to sensitize Mycobacterium tuberculosis to existing antibiotics. Through structure-based virtual screening of a compound library, we identified novel small-molecule inhibitors of M. tuberculosis uracil\u2013DNA glycosylase (MtbUng), an enzyme essential for the repair of DNA damage inflicted by macrophage-produced reactive nitrogen species. Experimental validation revealed that four derivatives of usnic acid, a lichen-derived metabolite, significantly inhibited MtbUng activity, with the most potent compound, OL10-88-1, exhibiting IC50 26 \u00b1 7 \u00b5M. Molecular docking suggests that OL10-88-1 inhibits MtbUng by occupying both the active site and the DNA-binding groove, thereby disrupting multiple steps of uracil recognition. The compounds also showed variable inhibitory activity against uracil\u2013DNA glycosylases from Escherichia coli, humans, and vaccinia virus. Our findings establish that the compound could potentially be used in combination therapies to enhance the efficacy of current anti-TB drugs by exploiting the vulnerability of DNA-repair-deficient mycobacteria.<\/jats:p>","DOI":"10.3390\/ijms27041954","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T12:59:16Z","timestamp":1771419556000},"page":"1954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Usnic Acid Derivatives as Inhibitors of Mycobacterium tuberculosis Uracil\u2013DNA Glycosylase"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2798-2844","authenticated-orcid":false,"given":"Aleksandr S.","family":"Filimonov","sequence":"first","affiliation":[{"name":"N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 Lavrentieva Ave., Novosibirsk 630090, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5619-2708","authenticated-orcid":false,"given":"Maria V.","family":"Zateeva","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8 Lavrentieva Ave., Novosibirsk 630090, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8643-8075","authenticated-orcid":false,"given":"Grigory V.","family":"Mechetin","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8 Lavrentieva Ave., Novosibirsk 630090, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8627-3453","authenticated-orcid":false,"given":"Olga A.","family":"Luzina","sequence":"additional","affiliation":[{"name":"N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 Lavrentieva Ave., Novosibirsk 630090, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4501-5113","authenticated-orcid":false,"given":"Chatchakorn","family":"Eurtivong","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8248-4218","authenticated-orcid":false,"given":"Suat","family":"Sari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3647-6591","authenticated-orcid":false,"given":"Anton V.","family":"Endutkin","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8 Lavrentieva Ave., Novosibirsk 630090, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4174-9512","authenticated-orcid":false,"given":"J\u00f3hannes","family":"Reynisson","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Keele University, Hornbeam Building, Staffordshire ST5 5BG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4083-9324","authenticated-orcid":false,"given":"Konstantin P.","family":"Volcho","sequence":"additional","affiliation":[{"name":"N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 Lavrentieva Ave., Novosibirsk 630090, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nariman F.","family":"Salakhutdinov","sequence":"additional","affiliation":[{"name":"N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 Lavrentieva Ave., Novosibirsk 630090, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitry O.","family":"Zharkov","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8 Lavrentieva Ave., Novosibirsk 630090, Russia"},{"name":"Department of Natural Sciences, Novosibirsk State University, 2 Pirogova St., Novosibirsk 630090, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025). 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