N-Leucinyl Benzenesulfonamides as Structurally Simplified Leucyl-tRNA Synthetase Inhibitors

A human leucyl-tRNA synthetase as an anticancer target

Several aminoacyl-tRNA synthetases have been reported to be overexpressed for charging essential aminoacyl-tRNAs in many cancer types. In this study, we aimed to explore the potential role of leucyl-tRNA synthetase (LARS) as an anticancer target. MTT assay was performed to screen inhibitors to human LARS (hsLARS) from compounds AN2690 and its derivatives, compounds 1-6, in U2OS and SKOV3 cells....

Discovery of Novel Oral Protein Synthesis Inhibitors of Mycobacterium tuberculosis That Target Leucyl-tRNA Synthetase

The recent development and spread of extensively drug-resistant and totally drug-resistant resistant (TDR) strains of Mycobacterium tuberculosis highlight the need for new antitubercular drugs. Protein synthesis inhibitors have played an important role in the treatment of tuberculosis (TB) starting with the inclusion of streptomycin in the first combination therapies. Although parenteral aminog...

Leucyl-tRNA synthetase controls TORC1 via the EGO complex.

The target of rapamycin complex 1 (TORC1) is an essential regulator of eukaryotic cell growth that responds to growth factors, energy levels, and amino acids. The mechanisms through which the preeminent amino acid leucine signals to the TORC1-regulatory Rag GTPases, which activate TORC1 within the yeast EGO complex (EGOC) or the structurally related mammalian Rag-Ragulator complex, remain elusi...

Prospects for aminoacyl-tRNA synthetase inhibitors as new antimicrobial agents.

C-7 modified flavonoids as novel tyrosyl-tRNA synthetase inhibitors

Twenty C-7modified flavonoids were designed and synthesized. Biological evaluation in vitro indicated that compounds generated by SYBYL-X with high scores also showed good inhibitory activities against TyrRS. Compounds containing the nargenin core exhibit better enzyme inhibitory activities than other flavonoid cores, with (S)-5-hydroxy-40-hydroxy-7-(2-morpholino-2-oxoethoxy)-2,3-dihydroflavone...