1. 10-DEBC Hydrochloride as a Promising New Agent against Infection of
- Author
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Da-Gyum, Lee, Hye-Jung, Kim, Youngsun, Lee, Jung-Hyun, Kim, Yoohyun, Hwang, Jeongyeop, Ha, and Sungweon, Ryoo
- Subjects
10-DEBC ,drug resistance ,Mycobacterium abscessus ,nonreplicating condition ,Macrophages ,Mycobacterium Infections, Nontuberculous ,bacterial infections and mycoses ,surrogate caseum binding assay ,Article ,Anti-Bacterial Agents ,Oxazines ,bacteria ,Humans ,Protein Kinase Inhibitors ,Proto-Oncogene Proteins c-akt - Abstract
Mycobacterium abscessus (M. abscessus) causes chronic pulmonary infections. Its resistance to current antimicrobial drugs makes it the most difficult non-tuberculous mycobacteria (NTM) to treat with a treatment success rate of 45.6%. Therefore, there is a need for new therapeutic agents against M. abscessus. We identified 10-DEBC hydrochloride (10-DEBC), a selective AKT inhibitor that exhibits inhibitory activity against M. abscessus. To evaluate the potential of 10-DEBC as a treatment for lung disease caused by M. abscessus, we measured its effectiveness in vitro. We established the intracellular activity of 10-DEBC against M. abscessus in human macrophages and human embryonic cell-derived macrophages (iMACs). 10-DEBC significantly inhibited the growth of wild-type M. abscessus and clinical isolates and clarithromycin (CLR)-resistant M. abscessus strains. 10-DEBC’s drug efficacy did not have cytotoxicity in the infected macrophages. In addition, 10-DEBC operates under anaerobic conditions without replication as well as in the presence of biofilms. The alternative caseum binding assay is a unique tool for evaluating drug efficacy against slow and nonreplicating bacilli in their native caseum media. In the surrogate caseum, the mean undiluted fraction unbound (fu) for 10-DEBC is 5.696. The results of an in vitro study on the activity of M. abscessus suggest that 10-DEBC is a potential new drug for treating M. abscessus infections.
- Published
- 2021