Zhao, Bing published the artcileDiscovery of thiosemicarbazone derivatives as effective New Delhi metallo-β-lactamase-1 (NDM-1) inhibitors against NDM-1 producing clinical isolates, Formula: C12H9NO, the publication is Acta Pharmaceutica Sinica B (2021), 11(1), 203-221, database is CAplus and MEDLINE.
In this study, structure-activity relationship based on thiosemicarbazone derivatives (E)-R1C(S)NHN=C(R2)(R3) (I) (R1 = phenylamino, Ph, cyclohexylamino, morpholin-4-yl, etc.; R2 = H, Me; R3 = Ph, pyridin-2-yl, 3,4,5-trimethoxyphenyl, etc.) was systematically characterized and their potential activities combined with meropenem (MEM) were evaluated. Compounds (I).HCl [R1 = piperazin-1-yl, R2 = H, R3 = 2-hydroxyphenyl (II); R1 = 4-methylpiperazin-1-yl, R2 = H, R3 = 2-hydroxyphenyl (III)] exhibited excellent activity against 10 NDM-pos. isolate clin. isolates in reversing MEM resistance. Further studies demonstrated that compounds II and III were uncompetitive NDM-1 inhibitors with Ki = 0.63 and 0.44μmol/L, resp. Mol. docking speculated that compounds II and III were most likely to bind in the allosteric pocket which would affect the catalytic effect of NDM-1 on the substrate meropenem. Toxicity evaluation experiment showed that no hemolysis activities were found even at concentrations of 1000 mg/mL against red blood cells. In vivo exptl. results showed that a combination of MEM and compound III was markedly effective in treating infections caused by NDM-1 pos. strain and prolonging the survival time of sepsis mice. The finding showed that compound III might be a promising lead in developing new inhibitor to treat NDM-1 producing superbug.
Acta Pharmaceutica Sinica B published new progress about 91-02-1. 91-02-1 belongs to pyridine-derivatives, auxiliary class Pyridine,Benzene,Ketone, name is Phenyl(pyridin-2-yl)methanone, and the molecular formula is C4H3Cl2N3, Formula: C12H9NO.
Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem