Center for Clinical Research, Masan National Tuberculosis Hospital, Changwon 51755, Korea.
New Drug Development Center, KBIO OSONG Medical Innovation Foundation, Cheongju 28160, Korea.
Int J Mol Sci. 2022 Jan 6;23(2):591. doi: 10.3390/ijms23020591.
() 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 . We identified 10-DEBC hydrochloride (10-DEBC), a selective AKT inhibitor that exhibits inhibitory activity against . To evaluate the potential of 10-DEBC as a treatment for lung disease caused by , we measured its effectiveness in vitro. We established the intracellular activity of 10-DEBC against in human macrophages and human embryonic cell-derived macrophages (iMACs). 10-DEBC significantly inhibited the growth of wild-type and clinical isolates and clarithromycin (CLR)-resistant 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 () for 10-DEBC is 5.696. The results of an in vitro study on the activity of suggest that 10-DEBC is a potential new drug for treating infections.
（）导致慢性肺部感染。它对现有抗菌药物的耐药性使其成为最难治疗的非结核分枝杆菌（NTM），治疗成功率仅为 45.6%。因此，需要新的治疗药物来对抗。我们鉴定出了 10-DEBC 盐酸盐（10-DEBC），这是一种选择性 AKT 抑制剂，对具有抑制活性。为了评估 10-DEBC 作为治疗由引起的肺部疾病的潜力，我们在体外测量了它的有效性。我们在人巨噬细胞和人胚胎细胞衍生的巨噬细胞（iMACs）中建立了 10-DEBC 针对的细胞内活性。10-DEBC 显著抑制了野生型和临床分离株以及克拉霉素（CLR）耐药株的生长。10-DEBC 的药效在感染的巨噬细胞中没有细胞毒性。此外，10-DEBC 在无氧条件下不复制，也可以在生物膜存在的情况下发挥作用。替代干酪素结合测定是一种独特的工具，用于评估在其天然干酪素介质中针对缓慢和非复制杆菌的药物疗效。在替代干酪素中，10-DEBC 的未结合的平均未稀释分数（）为 5.696。对 10-DEBC 活性的体外研究结果表明，它是一种治疗感染的潜在新药。
Zotero 插件
