{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T08:49:25Z","timestamp":1784105365835,"version":"3.55.0"},"reference-count":32,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T00:00:00Z","timestamp":1699228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Science Foundation","award":["21-45-00018"],"award-info":[{"award-number":["21-45-00018"]}]},{"name":"Russian Science Foundation","award":["82061138019"],"award-info":[{"award-number":["82061138019"]}]},{"name":"Russian Science Foundation","award":["2021YFA1300900"],"award-info":[{"award-number":["2021YFA1300900"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21-45-00018"],"award-info":[{"award-number":["21-45-00018"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82061138019"],"award-info":[{"award-number":["82061138019"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021YFA1300900"],"award-info":[{"award-number":["2021YFA1300900"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["21-45-00018"],"award-info":[{"award-number":["21-45-00018"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["82061138019"],"award-info":[{"award-number":["82061138019"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2021YFA1300900"],"award-info":[{"award-number":["2021YFA1300900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The World Health Organization (WHO) reports that tuberculosis (TB) is one of the top 10 leading causes of global mortality. The increasing incidence of multidrug-resistant TB highlights the urgent need for an intensified quest to discover innovative anti-TB medications In this study, we investigated four new derivatives from the quinoxaline-2-carboxylic acid 1,4-dioxide class. New 3-methylquinoxaline 1,4-dioxides with a variation in substituents at positions 2 and 6(7) were synthesized via nucleophilic aromatic substitution with amines and assessed against a Mycobacteria spp. Compound 4 showed high antimycobacterial activity (1.25 \u03bcg\/mL against M. tuberculosis) and low toxicity in vivo in mice. Selection and whole-genomic sequencing of spontaneous drug-resistant M. smegmatis mutants revealed a high number of single-nucleotide polymorphisms, confirming the predicted mode of action of the quinoxaline-2-carboxylic acid 1,4-dioxide 4 as a DNA-damaging agent. Subsequent reverse genetics methods confirmed that mutations in the genes MSMEG_4646, MSMEG_5122, and MSMEG_1380 mediate resistance to these compounds. Overall, the derivatives of quinoxaline-2-carboxylic acid 1,4-dioxide present a promising scaffold for the development of innovative antimycobacterial drugs.<\/jats:p>","DOI":"10.3390\/ph16111565","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T08:15:56Z","timestamp":1699258556000},"page":"1565","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Novel Derivatives of Quinoxaline-2-carboxylic Acid 1,4-Dioxides as Antimycobacterial Agents: Mechanistic Studies and Therapeutic Potential"],"prefix":"10.3390","volume":"16","author":[{"given":"Svetlana G.","family":"Frolova","sequence":"first","affiliation":[{"name":"Laboratory of Bacterial Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 119333 Moscow, Russia"},{"name":"Phystech School of Biological and Medical Physics, Moscow Institute of Physics and Technology (State University), 141701 Dolgoprudny, Russia"},{"name":"Institute for Regenerative Medicine, Department of Dermatology and Venereology, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6499-3908","authenticated-orcid":false,"given":"Aleksey A.","family":"Vatlin","sequence":"additional","affiliation":[{"name":"Laboratory of Bacterial Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 119333 Moscow, Russia"},{"name":"Institute of Ecology, Peoples\u2019 Friendship University of Russia (RUDN University), 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4296-5815","authenticated-orcid":false,"given":"Dmitry A.","family":"Maslov","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 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119021 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2015-0025","authenticated-orcid":false,"given":"Olga B.","family":"Bekker","sequence":"additional","affiliation":[{"name":"Laboratory of Bacterial Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 119333 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ksenia M.","family":"Klimina","sequence":"additional","affiliation":[{"name":"Laboratory of Bacterial Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 119333 Moscow, Russia"},{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency (Lopukhin FRCC PCM), 119435 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana V.","family":"Smirnova","sequence":"additional","affiliation":[{"name":"Laboratory of Bacterial Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 119333 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia M.","family":"Shnakhova","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine, Department of Dermatology and Venereology, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina K.","family":"Malyants","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency (Lopukhin FRCC PCM), 119435 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arseniy I.","family":"Lashkin","sequence":"additional","affiliation":[{"name":"Federal Research and Clinical Center of Physical-\u0421hemical Medicine, 119435 Moscow, Russia"},{"name":"Laboratory of Molecular Oncology, Department of Bioorganic 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