Zheng, Yun-Dan; Zhong, Tairan; Wu, Haiming; Li, Nan; Fang, Zuye; Cao, Linlin; Yin, Xing-Feng; He, Qing-Yu; Ge, Ruiguang; Sun, Xuesong published the artcile< Crizotinib shows antibacterial activity against Gram-positive bacteria by reducing ATP production and targeting the CTP synthase PyrG>, Product Details of C19H34O2, the main research area is crizotinib antibacterial activity bacteria ATP production CTP synthase PyrG; Gram-positive bacteria; crizotinib; drug repurposing; quantitative proteomics.
Infections caused by drug-resistant bacteria are a serious threat to public health worldwide, and the discovery of novel antibacterial compounds is urgently needed. Here, we screened an FDA-approved small-mol. library and found that crizotinib possesses good antimicrobial efficacy against Gram-pos. bacteria. Crizotinib was found to increase the survival rate of mice infected with bacteria and decrease pulmonary inflammation activity in an animal model. Furthermore, it showed synergy with clindamycin and gentamicin. Importantly, the Gram-pos. bacteria showed a low tendency to develop resistance to crizotinib. Mechanistically, quant. proteomics and biochem. validation experiments indicated that crizotinib exerted its antibacterial effects by reducing ATP production and pyrimidine metabolism A drug affinity responsive target stability study suggested crizotinib targets the CTP synthase PyrG, which subsequently disturbs pyrimidine metabolism and eventually reduces DNA synthesis. Subsequent mol. dynamics anal. showed that crizotinib binding occurs in close proximity to the ATP binding pocket of PyrG and causes loss of function of this CTP synthase. Crizotinib is a promising antimicrobial agent and provides a novel choice for the development of treatment for Gram-pos. infections.
Microbiology Spectrum published new progress about Acetyl-coenzyme A carboxylase inhibitors. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Product Details of C19H34O2.
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