Compound was previously identified by our team as a glycogen phosphorylase (GP) inhibitor with glucose-lowering activity and demonstrated to have protective effects against myocardial and cerebral ischemia. However, its impact on muscle function has not been clarified. This study is the first to evaluate the long-term effects of GP inhibitors on muscle function and metabolism.
View Article and Find Full Text PDFA novel series of erythrina derivatives as PARP-1/FTase inhibitors were synthesized, and evaluated for their biological activities. Compound T9 had excellent inhibitory effects on cell viability (A549: IC = 1.74 μM; A549/5-Fu: IC = 1.
View Article and Find Full Text PDFAs an essential marker of cancer treatment, PARP-1 inhibitors could effectively kill tumor cells through a mechanism known as synthetic lethality and are used to treat a variety of cancers. In order to explore novel PARP-1 inhibitors, a series of 22 novel erythrina derivatives were reported and preliminarily explored their mechanism of action. The antitumor activities against four human cancer cell lines including A549, OVCAR-3, HCT-116, and MCF-7 were evaluated, and the preliminary SARs were summarized.
View Article and Find Full Text PDFIn previous studies, we reported compound (5-chloro--(4-oxo-2,2-dipropyl-3,4-dihydro-2-benzo[][1,3]oxazin-6-yl)-1-indole-2-carboxamide) as a novel PYGB inhibitor, and found that it had better anti-ischemic brain injury activity. In this study, we established and validated a novel UHPLC-MS/MS method for the quantitative determination of compound in plasma, then applied the method to study the pharmacokinetic parameters and brain tissue distribution of compound in SD (Sprague-Dawley) rats after intravenous administration. The experimental results showed that the method met the validation requirements set by the US FDA in terms of linearity, accuracy, precision, and stability.
View Article and Find Full Text PDFThe high conservation of the three subtypes of glycogen phosphorylase (GP) presents significant challenges for specific inhibitor studies targeting GP. Our prior screening revealed that compound exhibited unequal inhibitory activity against the three GP subtypes, with a noticeable effect against brain GP (PYGB). The commercially available ingliforib demonstrated potent inhibitory activity specifically against liver GP (PYGL).
View Article and Find Full Text PDFGlycogen phosphorylase (GP) is a potential drug target. As the three subtypes of GP are highly conserved, it is difficult to research their specificity. However, compound inhibits the GP subtypes differently and was studied to aid in designing specific inhibitors.
View Article and Find Full Text PDFTo evaluate the effects of a novel glycogen phosphorylase inhibitor (NGPI) on cerebral ischemia-reperfusion injury (CIRI). Cerebral ischemia was induced in mice using a modified bilateral common carotid artery ligation model. To assess the effects of NGPI against CIRI, mice which had been administered with different doses of NGPI (1.
View Article and Find Full Text PDFBrain-type glycogen phosphorylase (PYGB) inhibitors are recognized as prospective drugs for treating ischemic brain injury. We previously reported compound as a novel glycogen phosphorylase inhibitor with brain-protective properties. In this study, we validated whether PYGB could be used as the therapeutic target for hypoxic-ischemic diseases and investigated whether compound exerts a protective effect against astrocyte hypoxia/reoxygenation (H/R) injury by targeting PYGB.
View Article and Find Full Text PDFBrain-type glycogen phosphorylase inhibitors are potential new drugs for treating ischemic brain injury. In our previous study, we reported compound as a novel brain-type glycogen phosphorylase inhibitor with cardioprotective properties. We also found that compound has high blood-brain barrier permeability through the ADMET prediction website.
View Article and Find Full Text PDFThe purpose of this study was to evaluate the effect of GP inhibitor as a potential pharmaceutical target on MI/R injury. Four different structural types of novel compounds (I, II, III, and IV) were designed and synthesized, obtaining 31 novel GP inhibitors. SAR studies revealed that the conjugates of 5-chloroindole with benzo six-membered heterocyclic were found to elevate the activity.
View Article and Find Full Text PDFOwing to the chronic nature of Type 2 diabetes mellitus, antidiabetic drugs must have long-lasting efficacy. Compound has a good inhibitory effect on acute hyperglycemia, but its long-term hypoglycemic effect has not been evaluated. Preliminary prediction and experimental pharmacokinetic results support the use of compound for long-term experiments.
View Article and Find Full Text PDFGlycogen phosphorylase (GP) is a key enzyme of glycogen catabolism, so it is significant to discover a new GP inhibitor. A series of benzazepinone derivatives were discovered as GP inhibitors with potent activity. Among these derivatives, compound showed significant potential against rabbit muscle GPa (IC = 0.
View Article and Find Full Text PDFA small set of indole-2-carboxamide derivatives identified from a high-throughput screening campaign has been described as a novel, potent, and glucose-sensitive inhibitors of glycogen phosphorylase a (GPa). Among this series of compounds, compound 2 exhibited moderate GP inhibitory activity (IC = 0.29 μM), good cellular efficacy (IC = 3.
View Article and Find Full Text PDFTo explore the molecular mechanisms of BAY R3401, four types of novel photoaffinity probes bearing different secondary tags were synthesized. Their potency for glycogenolysis was evaluated in primary human liver HL-7702 cells and HepG2 cells. Probe 2d showed the best activity in primary human liver HL-7702 cells and HepG2 cells, with IC values of 4.
View Article and Find Full Text PDFA procedure to measure the serum concentration of glycogen phosphorylase during acute myocardial infarction is presented. This method was based on the synthesis of photoaffinity probes, and used the semiquantitative protein electrophoretic mobility shift technique. Three novel photoaffinity probes bearing different secondary tags were synthesized.
View Article and Find Full Text PDFPSN-357, an effective glycogen phosphorylase (GP) inhibitor for the treatment for type 2 diabetics, is hampered in its clinical use by the poor selectivity between the GP isoforms in liver and in skeletal muscle. In this study, by the introduction of cholic acid, 9 novel potent and liver-targeted conjugates of PSN-357 were obtained. Among these conjugates, conjugate 6 exhibited slight GP inhibitory activity (IC = 31.
View Article and Find Full Text PDFTo study multi-fractal behavior of corroded steel surface, a range of fractal surfaces of corroded surfaces of Q235 steel were constructed by using the Weierstrass-Mandelbrot method under a high total accuracy. The multi-fractal spectrum of fractal surface of corroded steel was calculated to study the multi-fractal characteristics of the W-M corroded surface. Based on the shape feature of the multi-fractal spectrum of corroded steel surface, the least squares method was applied to the quadratic fitting of the multi-fractal spectrum of corroded surface.
View Article and Find Full Text PDFWei Sheng Wu Xue Bao
April 2014
Objective: The study was aimed at understanding the roles of polygalacturonases in the pathogenicity and the interaction between Rhizoctonia solani and rice.
Methods: According to the sequences of Rspg1 of R. solani deposited in GenBank, a pair of specific primers was designed.
J Nanosci Nanotechnol
July 2014
A new electron transfer dyad, covalently linked C70-corrole, was prepared via C70 and 10-(4-Formylaryl)-5,15-bis(pentafluorophenyl). The structures and the properties of the new material were investigated by HPLC, MALDI-TOF-MS, UV-Vis-NIR spectroscopy, NMR, fluorescence analysis and CV/DPV. The free-energy of C70-corrole calculated by employing the redox potentials and singlet excited-state energy suggested the possibility of electron transfer from the excited singlet state of corrole to the fullerene entity, which agreed with the results of the theoretical calculation.
View Article and Find Full Text PDFObjective: To carry out a nationwide epidemiologic survey on the neonates in urban hospitals with an attempt to understand the disease spectrum and treatment outcomes of hospitalized neonates in China.
Methods: The clinical data of 43,289 hospitalized neonates from 86 hospitals in 47 Chinese cities (22 provinces) between January 1, 2005 and December 31, 2005 were retrospectively analyzed.
Results: The male:female ratio was 1.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
February 2006
Antisense oligonucleotides (ASODN) for therapy is a genetic technology which is based on the base-complementary principle. DNA or RNA sequence synthesized by biotechnology is transferred into the target cells to form mRNA-DNA or mRNA-RNA double strand for inhibiting the expression of target genes. In this way we can control and treat some diseases.
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