2. Academic Validation
  3. Drug repurposing: An antidiabetic drug Ipragliflozin as Mycobacterium tuberculosis sirtuin-like protein inhibitor that synergizes with anti-tuberculosis drug isoniazid

Drug repurposing: An antidiabetic drug Ipragliflozin as Mycobacterium tuberculosis sirtuin-like protein inhibitor that synergizes with anti-tuberculosis drug isoniazid

  • Int J Biol Macromol. 2024 Dec;282(Pt 3):137003. doi: 10.1016/j.ijbiomac.2024.137003.
Junfeng Zhen 1,  Chao Zhang 2,  Tingting Huang 1,  Longxiang Xie 3,  Yaru Yan 1,  Shuangquan Yan 4,  Jinghan Zhang 1,  Hairong Huang 5,  Jianping Xie 6
Affiliations

Affiliations

  • 1 Institute of Modern Biopharmaceuticals, School of Life Sciences, Southwest University, Chongqing, China.
  • 2 National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory on Drug-Resistant Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing, China.
  • 3 Institute of Biomedical Informatics, Cell Signal Transduction Laboratory, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Huaihe Hospital, Henan University, Kaifeng, China.
  • 4 State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
  • 5 National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory on Drug-Resistant Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing, China. Electronic address: huanghairong@tb123.org.
  • 6 Institute of Modern Biopharmaceuticals, School of Life Sciences, Southwest University, Chongqing, China. Electronic address: georgex@swu.edu.cn.
PMID: 39481722 DOI: 10.1016/j.ijbiomac.2024.137003
Abstract

The surge of drug-resistant Mycobacterium tuberculosis (DR-TB) impedes the World Health Organization's efforts in ending TB and calls for new therapeutic formulations. M. tuberculosis sirtuin-like protein Rv1151c is a bifunctional Enzyme with both deacetylation and desuccinylation activities, which plays an important role in M. tuberculosis drug resistance and stress responses. Thus, it appears to be a promising target for the development of new TB therapeutics. In this study, we screened 31,057 ligand compounds from seven compound libraries in silico to identify inhibitors of Rv1151c. Ipragliflozin can bind to Rv1151c and interact stably. Ipragliflozin can change the acylation level of M. tuberculosis by inhibiting Rv1151c and effectively inhibit the growth of M. tuberculosis H37Rv and M. smegmatis. It can potentiate the first-front anti-TB drug isoniazid. As an antidiabetic drug, Ipragliflozin can be potentially included in the regimen to treat diabetes-tuberculosis comorbidity.

Keywords

Anti-TB drug target; Diabetes-tuberculosis comorbidity; Drug repositioning; Rv1151c; Virtual screening.

Figures
Products
Inhibitors & Agonists