216581-77-0Relevant academic research and scientific papers
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.
ALA hybrid 3-hydroxypyridone derivative as well as preparation method and application thereof
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, (2021/07/17)
The invention designs and synthesizes a novel anti-tumor active compound with iron chelating property and photosensitive activity based on the principles of reasonable drug design, drug-likeness and the like. The invention aims to provide a preparation me
Novel 2-Substituted 3-Hydroxy-1,6-dimethylpyridin-4(1 H)-ones as Dual-Acting Biofilm Inhibitors of Pseudomonas aeruginosa
Liu, Jun,Hou, Jin-Song,Li, Yi-Bin,Miao, Zhi-Ying,Sun, Ping-Hua,Lin, Jing,Chen, Wei-Min
, p. 10921 - 10945 (2020/11/09)
2-Heptyl-3-hydroxy-4(1H)-quinolone (PQS), a compound from P. aeruginosa, functions as both a quorum sensing (QS) regulator and a potent iron chelator to induce expression of pyoverdine and pyochelin which are involved in high-affinity iron transport syste
Synthesis, molecular modelling and biological studies of 3-hydroxy-pyrane-4-one and 3-hydroxy-pyridine-4-one derivatives as HIV-1 integrase inhibitors
Sirous, Hajar,Fassihi, Afshin,Brogi, Simone,Campiani, Giuseppe,Christ, Frauke,Debyser, Zeger,Gemma, Sandra,Butini, Stefania,Chemi, Giulia,Grillo, Alessandro,Zabihollahi, Rezvan,Aghasadeghi, Mohammad R.,Saghaie, Lotfollah,Memarian, Hamid R.
, p. 755 - 770 (2019/11/02)
Background: Despite the progress in the discovery of antiretroviral compounds for treating HIV-1 infection by targeting HIV integrase (IN), a promising and well-known drug target against HIV-1, there is a growing need to increase the armamentarium against
New fluorescent rosamine chelator showing promising antibacterial activity against Gram-positive bacteria
Novais, ?ngela,Moniz, Tania,Rebelo, Ana Rita,Silva, Ana M.G.,Rangel, Maria,Peixe, Luísa
, p. 341 - 349 (2018/06/01)
The restricted number of antibiotics to treat infections caused by common multidrug resistant bacterial pathogens in the clinical setting demands a continuous search for new molecules with antibacterial properties. Bacterial iron deprivation represents a
Structure-Activity Relationships in Metal-Binding Pharmacophores for Influenza Endonuclease
Credille, Cy V.,Dick, Benjamin L.,Morrison, Christine N.,Stokes, Ryjul W.,Adamek, Rebecca N.,Wu, Nicholas C.,Wilson, Ian A.,Cohen, Seth M.
, p. 10206 - 10217 (2018/11/23)
Metalloenzymes represent an important target space for drug discovery. A limitation to the early development of metalloenzyme inhibitors has been the lack of established structure-activity relationships (SARs) for molecules that bind the metal ion cofactor(s) of a metalloenzyme. Herein, we employed a bioinorganic perspective to develop an SAR for inhibition of the metalloenzyme influenza RNA polymerase PAN endonuclease. The identified trends highlight the importance of the electronics of the metal-binding pharmacophore (MBP), in addition to MBP sterics, for achieving improved inhibition and selectivity. By optimization of the MBPs for PAN endonuclease, a class of highly active and selective fragments was developed that displays IC50 values 50 values of ～10 nM, illustrating the utility of a metal-centric development campaign in generating highly active and selective metalloenzyme inhibitors.
Novel hydroxypyridinone compounds as well as preparation method and application thereof
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, (2018/07/30)
The invention belongs to the field of medicines and discloses novel hydroxypyridinone compounds as well as a preparation method and an application thereof. The compounds have the chemical structure shown in a formula (I), (II) or (III), wherein R1 is prop
CONJUGATES AND THEIR USES IN MOLECULAR IMAGING
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, (2014/03/24)
The present invention relates to bifunctional compounds, the bifunctional compounds for use in molecular imaging and therapy, methods of molecular imaging using the bifunctional compounds and kits including the bifunctional compounds for use molecular imaging. The bifunctional compounds have a tripodal hydroxypyridinone chelating portion and may be conjugated to a targeting group so that the compounds target specific cells or tissues in a subject.
Prediction of 3-hydroxypyridin-4-one (HPO) log K1 values for Fe(iii)
Chen, Yu-Lin,Barlow, Dave J.,Kong, Xiao-Le,Ma, Yong-Min,Hider, Robert C.
, p. 10784 - 10791 (2013/01/14)
As a means to aid in the design of 3-hydroxypyridin-4-ones (HPOs) intended for use as therapeutic Fe3+ chelating agents, a novel methodology has been developed using quantum mechanical (QM) calculations for predicting the iron binding affinities of the compounds (more specifically, their log K 1 values). The reported/measured HPO log K1 values were verified through their correlation with the corresponding sum of the compounds' ligating group pKa values. Using a training set of eleven HPOs with known log K1 values, reliable predictions are shown to be obtained with QM calculations using the B3LYP/6-31+G(d)/CPCM model chemistry (with Bondi radii, and water as solvent). With this methodology, the observed log K 1 values for the training set compounds are closely matched by the predicted values, with the correlation between the observed and predicted values giving r2 = 0.9. Predictions subsequently made by this method for a test set of 42 HPOs of known log K1 values gave predicted values accurate to within ±0.32 log units. In order to further investigate the predictive power of the method, four novel HPOs were synthesised and their log K1 values were determined experimentally. Comparison of these predicted log K1 values against the measured values gave absolute deviations of 0.22 (13.87 vs. 14.09), 0.02 (14.31 vs. 14.29), 0.12 (14.62 vs. 14.50), and 0.13 (15.04 vs. 15.17). The prediction methodology reported here is the first to be provided for predicting the absolute log K1 values of iron-chelating agents in the absence of pKa values.
Synthesis, iron(III)-binding affinity and in vitro evaluation of 3-hydroxypyridin-4-one hexadentate ligands as potential antimicrobial agents
Xu, Bo,Kong, Xiao-Le,Zhou, Tao,Qiu, Di-Hong,Chen, Yu-Lin,Liu, Mu-Song,Yang, Rong-Hua,Hider, Robert C.
scheme or table, p. 6376 - 6380 (2011/12/02)
Iron is a critical element for the survival of bacteria. We have designed and synthesized two novel 3-hydroxypyridin-4-one hexadentate ligands with high affinity for iron(III), which disrupt bacterial iron absorption. Biological studies demonstrate that these two chelators have significant inhibitory effect against both Gram-positive and Gram-negative bacteria, and therefore have potential as antimicrobial agents.
