{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T21:05:50Z","timestamp":1763499950927,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T00:00:00Z","timestamp":1714176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","doi-asserted-by":"publisher","award":["EXPL\/SAU-INF\/1097\/2021","UIDB\/04138\/2020","UIDP\/04138\/2020"],"award-info":[{"award-number":["EXPL\/SAU-INF\/1097\/2021","UIDB\/04138\/2020","UIDP\/04138\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT (via Imed ULisboa)","doi-asserted-by":"publisher","award":["EXPL\/SAU-INF\/1097\/2021","UIDB\/04138\/2020","UIDP\/04138\/2020"],"award-info":[{"award-number":["EXPL\/SAU-INF\/1097\/2021","UIDB\/04138\/2020","UIDP\/04138\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Tuberculosis (TB) continues to be a major global health challenge and a leading cause of death from infectious diseases. Inspired by the results from a previous work by our group on antimycobacterial N-alkylnitrobenzamides, which are structurally related to the nitrobenzamide family of decaprenylphosphoryl-\u03b2-d-ribose oxidase (DprE1) inhibitors, the present study explored a broad array of substituted benzamides. We particularly focused on previously unexplored 3,5-dinitrobenzamide derivatives. Starting with 3,5-dinitrobenzoic acid, we synthesized a diverse library of amides, incorporating both linear and cyclic amine moieties and also assessed the impact of terminal aromatic groups connected through ether, ester, or amide bonds on the bioactivity of the compounds. The synthesis primarily utilized nucleophilic addition\/elimination, SN2, and Mitsunobu reactions. The activity was impacted mainly by two structural features, the addition of an aromatic moiety as a terminal group and the type of linker. The most interesting compounds (c2, d1, and d2, MIC = 0.031 \u03bcg\/mL) exhibited activities against Mycobacterium Tuberculosis (Mtb) H37Rv comparable to isoniazid. Complementary computational studies helped elucidate potential interactions with DprE1, enhancing our understanding of the molecular basis of their action. Our findings suggest that the most active compounds provide a promising foundation for the continued development of new antimycobacterial agents.<\/jats:p>","DOI":"10.3390\/ph17050559","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T10:33:31Z","timestamp":1714559611000},"page":"559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Development of New Drugs to Treat Tuberculosis Based on the Dinitrobenzamide Scaffold"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8966-8415","authenticated-orcid":false,"given":"Tiago","family":"Delgado","sequence":"first","affiliation":[{"name":"Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3865-5913","authenticated-orcid":false,"given":"Jo\u00e3o P.","family":"Pais","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"},{"name":"Faculdade de Farm\u00e1cia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9602-1516","authenticated-orcid":false,"given":"David","family":"Pires","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"},{"name":"Faculdade de Farm\u00e1cia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"}]},{"given":"Filipe G. A.","family":"Estrada","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"},{"name":"Faculdade de Farm\u00e1cia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5790-9181","authenticated-orcid":false,"given":"Rita C.","family":"Guedes","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"},{"name":"Faculdade de Farm\u00e1cia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5934-0198","authenticated-orcid":false,"given":"Elsa","family":"Anes","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"},{"name":"Faculdade de Farm\u00e1cia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6847-4830","authenticated-orcid":false,"given":"Luis","family":"Constantino","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"},{"name":"Faculdade de Farm\u00e1cia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,27]]},"reference":[{"key":"ref_1","unstructured":"(2023). Global Tuberculosis Report 2023, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"350","DOI":"10.3389\/fped.2019.00350","article-title":"Immune Response to Mycobacterium tuberculosis: A Narrative Review","volume":"7","author":"Lodi","year":"2019","journal-title":"Front. 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