ABSTRACT
The protein proteolysis-targeting chimeras (PROTAC) are a kind of bifunctional compound that can recruit target proteins and degrade the enzyme of target proteins. The mechanism of PROTAC is using the ubiquitin-proteasome pathway to degrade target protein specifically. Because of its potential to target non-proprietary proteins and to play roles in drug resistance, PROTAC has attracted wide attention. This review summarizes the application of small molecule PROTAC in previous studies of different targets, such as nuclear proteins, membrane proteins and cytoplasmic proteins.
ABSTRACT
NADPH oxidases (NOXs) are the key enzymes of redox signaling in vivo and also the main source of reactive oxygen species (ROS) in the body. ROS plays a role of double-edged sword. On the one hand, ROS, at the level of physiological amount, has the effect of immune defense and also acts as a second messenger involved in the regulation of cellular signaling pathways. On the other hand, excessive ROS can cause oxidative stress, leading to the disorder of cellular functions. Recently, studies showed that ROS plays an important role in acceleration of some pathological reactions such as inflammation, fibrosis and tumor formation. As a major source of ROS, NOX has become a popular target in treating oxidative stress, inflammation, fibrosis and tumor. Herein, the role of NOX in these pathological processes and the research progress of NOX inhibitors are reviewed.
ABSTRACT
Cyclin-dependent kinase-5 (Cdk5) is a kind of Ser/Thr kinases in the signaling pathway, which regulates the neural development. The recent studies have confirmed that hyperactivation of Cdk5 is closely associated with the evolution, progression and apoptosis of tumors. The Cdk5 inhibitors have been extensively studied in the drug discovery against cancer. The structure features of these inhibitors and molecular mechanisms of their activities have provided clues for the drug development. In the second generation Cdk5 inhibitors, the ATP-binding pocket, a highly conserved site, has been targeted in the drug design in most cases. In addition, a growing number of peptides has been generated by targeting the protein/protein interfaces of Cdk5.
ABSTRACT
p70 ribosomal protein S6 kinase (p70S6K), an important member of AGC family, is a kind of multifunctional Ser/Thr kinases, which plays an important role in mTOR signaling cascade. The p70 ribosomal protein S6 kinase is closely associated with diverse cellular processes such as protein synthesis, mRNA processing, glucose homeostasis, cell growth and apoptosis. Recent studies have highlighted the important role of S6K in cancer, which arose interests of scientific researchers for the design and discovery of anti-cancer agents. Herein, the mechanisms of S6K and available inhibitors are reviewed.
Subject(s)
Humans , Antineoplastic Agents , Protein Kinase Inhibitors , Chemistry , Ribosomal Protein S6 Kinases, 70-kDa , Metabolism , Signal Transduction , TOR Serine-Threonine KinasesABSTRACT
OBJECTIVE@#To determine the relationship between the nitroglycerin tolerance and the stimulation of radical oxygen species (ROS) production, and the therapeutical effect of 3,4,5,6-tetrahydroxyxanthone.@*METHODS@#Vasodilator responses to nitroglycerin were examined in the isolated thoracic aorta. The contents of ROS,and cGMP were determined in the cultured human umbilical vein endothelial cells.@*RESULTS@#3,4,5,6-tetrahydroxyxanthone could significantly reduce the inhibition of relaxation by nitroglycerin. 3,4,5,6-tetrahydroxyxanthone could significantly inhibit the ROS increase and increase the cGMP level.@*CONCLUSION@#Nitroglycerin tolerance is associated with the stimulation of ROS production,and the reversal of nitroglycerin tolerance with 3,4,5,6-tetrahydroxyxanthone is related to the reduction of ROS.
Subject(s)
Animals , Humans , Male , Rats , Antioxidants , Pharmacology , Aorta, Thoracic , Cell Biology , Cells, Cultured , Drug Tolerance , Endothelium, Vascular , Cell Biology , Nitroglycerin , Pharmacology , Oxidative Stress , Rats, Sprague-Dawley , Reactive Oxygen Species , Metabolism , Umbilical Veins , Cell Biology , Xanthones , PharmacologyABSTRACT
<p><b>AIM</b>To study the active constituents of Swertia davidi Franch.</p><p><b>METHODS</b>Column chromatographies on silica gel, Sephadex LH-20 and Diaion-201 et al. were used to isolate and purify the chemical components. Their structures were identified by UV, IR, MS, NMR and 2D-NMR.</p><p><b>RESULTS</b>These compounds were elucidated as 8-O-beta-D-glucopyranosyl-1, 3, 5-trihydroxyxanthone (I), 5-O-beta-D-glucopyranosyl-1, 8-dihydroxy-3-methoxyxanthone (II), 5-O-beta-D-glucopyranosyl-1, 3, 8-trihydroxyxanthone (III) and swertamarin (IV).</p><p><b>CONCLUSION</b>Compound III is a new xanthone glucoside. The other compounds were isolated from this plant for the first time.</p>
Subject(s)
Glucosides , Chemistry , Molecular Conformation , Molecular Structure , Plants, Medicinal , Chemistry , Swertia , Chemistry , Xanthones , ChemistryABSTRACT
<p><b>AIM</b>To study the chemical constituents of Polygala aureocauda Dunn..</p><p><b>METHODS</b>Chemical compounds were isolated by column chromatography and their structures were determined mainly by spectroscopic means (UV, IR, MS, 1HNMR, 13CNMR, HMQC, HMBC).</p><p><b>RESULTS</b>Three compounds were isolated and identified as 3-hydroxy-1,4-dimethoxyxanthone (I), 1, 7-dihydroxy-2, 3-methylendioxyxanthone (II), 7-hydroxy-1-methoxy-2, 3-methylendioxyxanthone (III).</p><p><b>CONCLUSION</b>Compounds I-III were isolated from Polygala aureocauda Dunn. for the first time, whereas compound I is a new xanthone.</p>
Subject(s)
Molecular Conformation , Molecular Structure , Plant Roots , Chemistry , Plants, Medicinal , Chemistry , Polygala , Chemistry , Xanthones , ChemistryABSTRACT
<p><b>AIM</b>To study the active constituents of Swertia davidi Franch.</p><p><b>METHODS</b>Chemical components were isolated by column chromatography and their structures were established mainly by spectroscopic means (UV, IR, NMR, 2D-NMR, MS).</p><p><b>RESULTS</b>Three substances were identified as 2,5-dimethoxyl-1, 4-dicarboxyl benzene (VIII), 1,5,8-trihydroxyl-3,4-dimethoxyl xanthone (IX) and 1,8-dihydroxyl-3-(3'-hydroxyl-butoxy) xanthone (X).</p><p><b>CONCLUSION</b>Compounds VIII and IX were isolated from Swertia davidi Franch, for the first time, whereas compound X is a new xanthone, named daviditin B with antioxygenated activity in vitro.</p>
Subject(s)
Antioxidants , Chemistry , Molecular Conformation , Molecular Structure , Plants, Medicinal , Chemistry , Swertia , Chemistry , Xanthones , ChemistryABSTRACT
<p><b>AIM</b>To study the active constituents of Swertia davidi Franch..</p><p><b>METHODS</b>Chromatography was used to isolate and purify the chemical components, their structures were identified by spectral analysis.</p><p><b>RESULTS</b>Three compounds were identified as 1,7-dihydroxy-3,8-dimethoxyxanthone (gentiacaulein) (V), 1,8-dihydroxy-3,7-dimethoxyxanthone (methylswertianin) (VI) and 1,8-dihydroxy-3,4,7-trimethoxyxanthone (VII).</p><p><b>CONCLUSION</b>Compound VII is a novel xanthone, named daviditin A, the others were isolated from Swertia davidi Franch. for the first time.</p>