Dual GSK-3β/HDAC Inhibitors Enhance the Efficacy of Macrophages to Control <i>Mycobacterium tuberculosis</i> Infection.

ABSTRACT: Multitarget drug discovery, including host-directed therapy, is particularly promising for tuberculosis (TB) due to the resilience of Mycobacterium tuberculosis (Mtb) as well as the complexity of the host's immune response. In this proof-of-concept study, we used high-content imaging to test a novel panel of dual glycogen synthase kinase 3 beta (GSK-3β) and histone deacetylase (HDAC) 1 and 6 inhibitor candidates for their efficacy in reducing the growth of green fluorescent protein (GFP)-expressing mycobacteria in human primary macrophages. We demonstrate that all ten test compounds, also including the GSK-3β inhibitor SB415286, exhibit an antimycobacterial effect of 20-60% at low micromolar doses and are non-toxic to host cells. Mtb growth showed a positive correlation with the res

SUBMITTER: Kalsum S 

PROVIDER: S-EPMC12024928 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature