89539-51-5Relevant articles and documents
New Pqs Quorum Sensing System Inhibitor as an Antibacterial Synergist against Multidrug-Resistant Pseudomonas aeruginosa
Liu, Jun,Hou, Jin-Song,Chang, Yi-Qun,Peng, Li-Jun,Zhang, Xiao-Yi,Miao, Zhi-Ying,Sun, Ping-Hua,Lin, Jing,Chen, Wei-Min
, p. 688 - 709 (2022/01/12)
Development of new bacterial biofilm inhibitors as antibacterial synergists is an effective strategy to solve the resistance of Pseudomonas aeruginosa. In this paper, a series of 3-hydroxy-pyridin-4(1H)-ones were synthesized and evaluated, and the hit compound (20p) was identified with the effects of inhibiting the production of pyocyanin (IC50 = 8.6 μM) and biofilm formation (IC50 = 4.5 μM). Mechanistic studies confirmed that 20p inhibits the formation of bacterial biofilm by inhibiting the expression of pqsA, blocking pqs quorum sensing system quinolone biosynthesis. Moreover, we systematically investigated the bactericidal effects of combining currently approved antibiotics for CF including tobramycin, ciprofloxacin, and colistin E with 20p, which showed obvious antibacterial synergy to overcome antibiotics resistance in multidrug-resistant P. aeruginosa biofilms. The result indicates that compound 20p may be used in the future as a potentially novel antibacterial synergist candidate for the treatment of P. aeruginosa infections.
Pyridone hexa-alkyne amine modified derivative and preparation method and application thereof
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Paragraph 0085; 0088, (2021/03/30)
The invention relates to a pyridone hexa-alkyne amine modified derivative as shown in a formula (I) and a pharmaceutically acceptable salt thereof, a preparation method thereof, application of the pyridone hexa-alkyne amine modified derivative or the pharmaceutically acceptable salt thereof to preparation of drugs for preventing or treating related diseases, especially Alzheimer's disease and Parkinson's disease, by inhibiting monoamine oxidase, chelating metal iron ions, resisting Abeta and resisting oxidation. According to the invention, a series of novel single-molecule multi-target anti-ADactive compounds are synthesized, and pyridone derivatives with iron ion chelating activity and propynylamine with MAOB inhibitory activity are creatively and organically combined together, so that the compounds have remarkable advantages on Alzheimer's disease with complex pathogenesis; and the combined molecules are far superior to CP20 (deferiprone) in the aspect of iron ion chelating activity.
Functionality study of chalcone-hydroxypyridinone hybrids as tyrosinase inhibitors and influence on anti-tyrosinase activity
Singh, L. Ravithej,Chen, Yu-Lin,Xie, Yuan-Yuan,Xia, Wei,Gong, Xing-Wen,Hider, Robert C.,Zhou, Tao
, p. 1562 - 1567 (2020/08/07)
In an attempt to synthesise new tyrosinase inhibitors, we designed and synthesised a series of chalcone-hydroxypyridinone hybrids as potential tyrosinase inhibitors adopting strategic modifications of kojic acid. All the newly synthesised compounds were characterised by NMR and mass spectrometry. Initial screening of the target compounds demonstrated that compounds 1a, 1d, and 1n had relatively strong inhibitory activities against tyrosinase monophenolase, with IC50 values of 3.07 ± 0.85, 2.25 ± 0.8 and 2.75 ± 1.19 μM, respectively. The inhibitory activity against monophenolase was 6- to 8-fold higher than that of kojic acid. Compounds 1a, 1d, and 1n also showed inhibition of diphenolase, with IC50 values of 17.05 ± 0.07, 11.70 ± 0.03 and 19.3 ± 0.28 μM, respectively. The inhibition kinetics of diphenolase indicates that compounds 1a and 1d induce reversible inhibition on tyrosinase. Finally, we found that copper coordination should be one of the important inhibitory mechanism of these compounds in tyrosinase.
