No abstract

A screen of 37 compounds identified four inhibitors that exhibited dual on-target activity against Mycobacterium tuberculosis aminoacyl-tRNA synthetases.

No abstract

Staphylococcus aureus is one of the most dangerous pathogens commonly associated with high levels of morbidity and mortality. Sortase A is considered as a promising molecular target for the development of antistaphylococcal agents. Using hybrid virtual screening approach and FRET analysis, we have identified five compounds able to decrease the activity of sortase A by more than 50% at the concentration of 200 µM. The most promising compound was 2-(2-amino-3-chloro-benzoylamino)-benzoic acid which was able to inhibit S. aureus sortase A at the IC 50 value of 59.7 µM. This compound was selective toward sortase A compared to other four cysteine proteases – cathepsin L, cathepsin B, rhodesain, and the SARS-CoV2 main protease. Microscale thermophoresis experiments confirmed that this compound bound sortase A with K D value of 189 µM. Antibacterial and antibiofilm assays also confirmed high specificity of the hit compound against two standard and three wild-type, S. aureus hospital infection isolates. The effect of the compound on biofilms produced by two S. aureus ATCC strains was also observed suggesting that the compound reduced biofilm formation by changing the biofilm structure and thickness.

We propose a new deep learning DTA model 3DProtDTA, which utilises AlphaFold structure predictions in conjunction with the graph representation of proteins.

In this article, the derivatives of 3-quinoline carboxylic acid were studied as inhibitors of protein kinase CK2. Forty-three new compounds were synthesized. Among them 22 compounds inhibiting CK2 with IC 50 in the range from 0.65 to 18.2 mM were identified. The most active inhibitors were found among tetrazolo-quinoline-4-carboxylic acid and 2-aminoquinoline-3-carboxylic acid derivatives. KeywordsInhibitor, protein kinase CK2, tetrazolo[1,5-a]quinoline-4-carboxylic acid, 2-aminoquinoline-3-carboxylic acid, 2-chloroquinoline-3-carboxylic acid, 2-oxo-1,2-dihydroquinoline-3-carboxylic acid, 5-oxo-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-6-carboxylic acid History

No abstract

No abstract