Ngo, Huy X. published the artcilePotent 1,2,4-Triazino[5,6b]indole-3-thioether Inhibitors of the Kanamycin Resistance Enzyme Eis from Mycobacterium tuberculosis, Recommanded Product: 2-(Chloromethyl)-1-methylpiperidine hydrochloride, the main research area is triazinoindole thioether kanamycin resistance aminoglycoside acetyltransferase Eis Mycobacterium tuberculostatic; aminoglycoside resistance; antitubercular agent; combination therapy; high-throughput screen; structure-activity relationship (SAR).
A common cause of resistance to kanamycin (KAN) in tuberculosis is overexpression of the enhanced intracellular survival (Eis) protein. Eis is an acetyltransferase that multiacetylates KAN and other aminoglycosides, rendering them unable to bind the bacterial ribosome. By high-throughput screening, a series of substituted 1,2,4-triazino[5,6b]indole-3-thioether mols. were identified as effective Eis inhibitors. Herein, the authors purchased 17 and synthesized 22 new compounds, evaluated their potency, and characterized their steady-state kinetics. Four inhibitors were found not only to inhibit Eis in vitro, but also to act as adjuvants of KAN and partially restore KAN sensitivity in a Mycobacterium tuberculosis KAN-resistant strain in which Eis is upregulated. A crystal structure of Eis in complex with a potent inhibitor and Co-A shows that the inhibitors bind in the aminoglycoside binding site snugly inserted into a hydrophobic cavity. These inhibitors will undergo preclin. development as novel KAN adjuvant therapies to treat KAN-resistant tuberculosis.
ACS Infectious Diseases published new progress about Antibacterial agent resistance. 27483-92-7 belongs to class piperidines, name is 2-(Chloromethyl)-1-methylpiperidine hydrochloride, and the molecular formula is C7H15Cl2N, Recommanded Product: 2-(Chloromethyl)-1-methylpiperidine hydrochloride.
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem