{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T10:26:19Z","timestamp":1758709579810,"version":"3.41.2"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T00:00:00Z","timestamp":1701302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tuberculosis (TB) disease, caused by <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:italic>Mtb<\/jats:italic>) is the leading cause of death among people with human immunodeficiency virus (HIV) infection. No dual\u2010target drug is currently being used to simultaneously treat both infections. This work aimed to obtain new multitarget HIV\u2010TB agents, with the goal of optimizing treatments and preventing this coinfection. These compounds incorporate the structural features of azaaurones as anti\u2010<jats:italic>Mtb<\/jats:italic> and zidovudine (AZT) as the antiretroviral moiety. The azaaurone scaffold displayed submicromolar activities against <jats:italic>Mtb<\/jats:italic>, and AZT is a potent antiretroviral drug. Six derivatives were synthetically generated, and five were evaluated against both infective agents. Evaluations of anti\u2010HIV activity were carried out in HIV\u20101\u2010infected MT\u20104 cells and on endogenous HIV\u20101 reverse transcriptase (RT) activity. The H37Rv strain was used for anti\u2010<jats:italic>Mtb<\/jats:italic> assessments. Most compounds displayed potent antitubercular and moderate anti\u2010HIV activity. (<jats:italic>E<\/jats:italic>)\u2010<jats:bold>12<\/jats:bold> exhibited a promising multitarget profile with an MIC<jats:sub>90<\/jats:sub> of 2.82\u2009\u00b5M and an IC<jats:sub>50<\/jats:sub> of 1.98\u2009\u00b5M in HIV\u20101\u2010infected T lymphocyte cells, with an 84% inhibition of RT activity. Therefore, (<jats:italic>E<\/jats:italic>)\u2010<jats:bold>12<\/jats:bold> could be the first promising compound from a family of multitarget agents used to treat HIV\u2010TB coinfection. In addition, the compound could offer a prototype for the development of new strategies in scientific research to treat this global health issue.<\/jats:p>","DOI":"10.1002\/ardp.202300560","type":"journal-article","created":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T13:52:02Z","timestamp":1701352322000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["New azaaurone derivatives as potential multitarget agents in HIV\u2010TB coinfection"],"prefix":"10.1002","volume":"357","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5313-9466","authenticated-orcid":false,"given":"Debora I.","family":"Leite","sequence":"first","affiliation":[{"name":"Instituto de Tecnologia em F\u00e1rmacos, Laborat\u00f3rio de S\u00edntese de F\u00e1rmacos (LASFAR) Funda\u00e7\u00e3o Oswaldo Cruz  Rio de Janeiro Brasil"}]},{"given":"Andre","family":"Campani\u00e7o","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia Universidade de Lisboa  Lisbon Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8290-8167","authenticated-orcid":false,"given":"Pedro A. 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