ABSTRACT
Fibroblast growth factor receptors (FGFRs) have emerged as promising targets for anticancer therapy. In this study, we synthesized and evaluated the biological activity of 66 pyrazolo[3,4-
ABSTRACT
Human 5-lipoxygenase (5-LOX) is a well-validated drug target and its inhibitors are potential drugs for treating leukotriene-related disorders. Our previous work on structural optimization of the hit compound 2 from our in-house collection identified two lead compounds, 3a and 3b, exhibiting a potent inhibitory profile against 5-LOX with IC50 values less than 1 µmol/L in cell-based assays. Here, we further optimized these compounds to prepare a class of novel pyrazole derivatives by opening the fused-ring system. Several new compounds exhibited more potent inhibitory activity than the lead compounds against 5-LOX. In particular, compound 4e not only suppressed lipopolysaccharide-induced inflammation in brain inflammatory cells and protected neurons from oxidative toxicity, but also significantly decreased infarct damage in a mouse model of cerebral ischemia. Molecular docking analysis further confirmed the consistency of our theoretical results and experimental data. In conclusion, the excellent in vitro and in vivo inhibitory activities of these compounds against 5-LOX suggested that these novel chemical structures have a promising therapeutic potential to treat leukotriene-related disorders.
ABSTRACT
<p><b>OBJECTIVE</b>To prepare vincristine sulphate loaded poly (butylcyanoacrylate) nanoparticles (VCR-PBCA-NPs) and to investigate the in vitro release charactersitics.</p><p><b>METHOD</b>VCR-PBCA-NPs were prepared by emulsion polymerization method, and characterized for morphology, particle size, drug encapsulation efficiency and loading efficiency. The formulation was optimized using central composite design and response surface methodology. In vitro release study of VCR-PBCA-NPs was performed by dialysis technique. Model fitting was used to determine the kinetics and to discuss the mechanism.</p><p><b>RESULT</b>The nanoparticles were spherical and uniform with a mean diameter of (98.9 +/- 3.05) nm. The drug encapsulation efficiency and loading efficiency were (55.23 +/- 0.96)% and (7.87 +/- 0.11)%, respectively. In vitro release results showed that 63.66% of VCR was released from VCR-PBCA-NPs in 4 h, and the Weibull model fitted VCR release pattern best.</p><p><b>CONCLUSION</b>The VCR-PBCA-NPs prepared in this study showed sustained release compared with VCR solution.</p>
Subject(s)
Chemistry, Pharmaceutical , Methods , Cyanoacrylates , Delayed-Action Preparations , Chemistry , Drug Carriers , Chemistry , Drug Compounding , Methods , Emulsions , Enbucrilate , Chemistry , In Vitro Techniques , Nanoparticles , Chemistry , Particle Size , Vincristine , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To study plasma protein binding rate of bufalin.</p><p><b>METHOD</b>HPLC was employed to determine the concentration of bufalin. Plasma protein binding rate studies were conducted by equilibrium dialysis method. The influence of drug concentration and plasma in different species on plasma protein binding rate were studied.</p><p><b>RESULT</b>There was no significant difference in the plasma protein binding rates at low, middle and high bufalin concentrations in dilution medium. The protein binding rate of bufalin in human plasma was higher than in the rat plasma.</p><p><b>CONCLUSION</b>Bufalin has higher protein binding extent with both rat plasma and human plasma.</p>
Subject(s)
Animals , Humans , Male , Rats , Blood Proteins , Chemistry , Bufanolides , Chemistry , Kinetics , Protein Binding , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To prepare and evaluate brucine-loaded polylacticacid nanoparticles (Bru-PLA-NPs).</p><p><b>METHOD</b>The Bru-PLA-NPs were prepared by solvent diffusion method. The physical, chemical properties and in vitro release behavior of the prepared Bru-PLA-NPs were evaluated, respectively.</p><p><b>RESULT</b>The mean particle size of the prepared Bru-PLA-NPs was 95 nm with polydispersity index of 0.362. The zeta potential was -15.68 mV. The mean loading and entrapment efficiency of Bru were 7% and 37%, respectively. Compared with Bru solution, an obvious sustained release behavior of Bru from Bru-PLA-NPs was observed in the in vitro release experiment.</p><p><b>CONCLUSION</b>The Bru-PLA-NPs prepared by solvent diffusion method exhibit small particle size, high Bru-loading efficiency, and obvious sustained release in vitro</p>
Subject(s)
Drug Carriers , Chemistry , Drug Delivery Systems , Methods , Drugs, Chinese Herbal , Chemistry , Kinetics , Lactic Acid , Chemistry , Nanoparticles , Chemistry , Particle Size , Polyesters , Polymers , Chemistry , Strychnine , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To investigate the stability of oridonin (ORI) solution for research and development of novel ORI prepartions.</p><p><b>METHOD</b>The effect of pH on the degradation rate of ORI was evaluated, the pH values of the oridonin solutions were adjusted to the setting pH, with 1 mol x L(-1) HCl or NaOH, respectively, and stored at room temperature for 60 h. The constant temperature method was applied to evaluate the stability of ORI solution at room temperature and at 4 degrees C.</p><p><b>RESULT</b>The pH-rate profile of ORI was V-shaped, and the pHm was 5. The t90 of ORI solution at room temperature was 53.2 h and 91.5 h at 4 degrees C CONCLUSION: The ORI solution is not stable. The pH-dependent degradation of ORI solution confirms to specific acid-base catalysis reaction.</p>