DOI: 10.1002/ardp.202300560 ISSN: 0365-6233

New azaaurone derivatives as potential multitarget agents in HIV‐TB coinfection

Debora I. Leite, Andre Campaniço, Pedro A. G. Costa, Isadora A. Correa, Luciana J. da Costa, Monica M. Bastos, Rui Moreira, Francisca Lopes, Audrey Jordaan, Digby F. Warner, Nubia Boechat
  • Drug Discovery
  • Pharmaceutical Science


Tuberculosis (TB) disease, caused by Mycobacterium tuberculosis (Mtb) is the leading cause of death among people with human immunodeficiency virus (HIV) infection. No dual‐target drug is currently being used to simultaneously treat both infections. This work aimed to obtain new multitarget HIV‐TB agents, with the goal of optimizing treatments and preventing this coinfection. These compounds incorporate the structural features of azaaurones as anti‐Mtb and zidovudine (AZT) as the antiretroviral moiety. The azaaurone scaffold displayed submicromolar activities against Mtb, and AZT is a potent antiretroviral drug. Six derivatives were synthetically generated, and five were evaluated against both infective agents. Evaluations of anti‐HIV activity were carried out in HIV‐1‐infected MT‐4 cells and on endogenous HIV‐1 reverse transcriptase (RT) activity. The H37Rv strain was used for anti‐Mtb assessments. Most compounds displayed potent antitubercular and moderate anti‐HIV activity. (E)‐12 exhibited a promising multitarget profile with an MIC90 of 2.82 µM and an IC50 of 1.98 µM in HIV‐1‐infected T lymphocyte cells, with an 84% inhibition of RT activity. Therefore, (E)‐12 could be the first promising compound from a family of multitarget agents used to treat HIV‐TB coinfection. In addition, the compound could offer a prototype for the development of new strategies in scientific research to treat this global health issue.

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