Нещодавно, була опублікована стаття, присвячена розробці інгібіторів аміноацил-тРНК синтетаз Mycobacterium tuberculosis із мультитаргетною дією.
Abstract:
Background: The most serious challenge in the treatment of tuberculosis is the multidrug resistance of Mycobacterium tuberculosis to existing antibiotics. As a strategy to overcome resistance we used a multitarget drug design approach. The purpose of the work was to discover dual-targeted inhibitors of mycobacterial LeuRS and MetRS with machine learning. Methods: The artificial neural networks were built using module nnet fro R 3.6.1. The inhibitory activity of compounds toward LeuRS and MetRS was investigated in aminoacylation assay. Results: Using a machine-learning approach, we identified dual-targeted inhibitors of LeuRS and MetRS among 2-(quinolin-2-ylsulfanyl)-acetamide derivatives. The most active compounds inhibits MetRS and LeuRS with IC50 values of 33 μM and 23.9 μM. Conclusion: 2-(Quinolin-2-ylsulfanyl)-acetamide scaffold can be useful for further research.