Kovalenko, Oksana P. published the artcileDual-target inhibitors of mycobacterial aminoacyl-tRNA synthetases among N-benzylidene-N′-thiazol-2-yl-hydrazines, Category: isoquinoline, the main research area is benzylidenyl thiazolyl hydrazine preparation; aminoacyltRNA synthetase inhibition tuberculostatics mol docking SAR.
Effective treatment of tuberculosis is challenged by the rapid development of Mycobacterium tuberculosis (Mtb) multidrug resistance that presumably could be overcome with novel multi-target drugs. Aminoacyl-tRNA synthetases (AARSs) are an essential part of protein biosynthesis machinery and attractive targets for drug discovery. Here, we exptl. verify a hypothesis of simultaneous targeting of structurally related AARSs by a single inhibitor. We previously identified a new class of mycobacterial leucyl-tRNA synthetase inhibitors, N-benzylidene-N′-thiazol-2-yl-hydrazines. Mol. docking of a library of novel N-benzylidene-N′-thiazol-2-yl-hydrazine derivatives into active sites of M. tuberculosis LeuRS (MtbLeuRS) and MetRS (MtbMetRS) resulted in a panel of the best ranking compounds, which were then evaluated for enzymic potency. Screening data revealed 11 compounds active against MtbLeuRS and 28 compounds active against MtbMetRS. The hit compounds display dual inhibitory potency as demonstrated by IC50 values for both enzymes. Compound I is active against Mtb H37Rv cells in in vitro bioassays.
MedChemComm published new progress about Aminoacyl-tRNA synthetase inhibitors. 86-51-1 belongs to class isoquinoline, name is 2,3-Dimethoxybenzaldehyde, and the molecular formula is C9H10O3, Category: isoquinoline.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem