ABSTRACT
With the continuous development in microfluidic fabrication technology, microfluidic analysis has evolved from a concept to one of research frontiers in last twenty years. The research of enzymes and enzyme inhibitors based on microfluidic devices has also made great progress. Microfluidic technology improved greatly the analytical performance of the research of enzymes and enzyme inhibitors by reducing the consumption of reagents, decreasing the analysis time, and developing automation. This review focuses on the development and classification of enzymes and enzyme inhibitors research based on microfluidic devices.
Subject(s)
Enzyme Inhibitors/metabolism , Enzymes/metabolism , Microfluidic Analytical Techniques/methods , Microfluidics/methodsABSTRACT
5-Aryl-4-cyano-1H-1, 2, 3-triazoles bearing a variety of substituting groups on 5-phenyl were synthesized. Their structures were established by MS, IR and 1H NMR spectra. The crystal structures of compounds 3f and 3m were determined by X-ray diffraction analysis. The active H of the triazole was on 1-N from the crystal structures. The compounds, designed as HER2 tyrosine kinase inhibitors, were screened for bioactivity of growth-inhibition of breast cancer MDA-MB-453 cells. The lowest IC50 value of inhibiting HER2 tyrosine kinase phosphorylation in breast cancer cells is 6.6 micromol x L(-1). The inhibiting-growth of breast cancer cells was enhanced from electron-drawing groups joining 5-phenyl on the triazole.
Subject(s)
Breast Neoplasms/pathology , Protein-Tyrosine Kinases/antagonists & inhibitors , Receptor, ErbB-2/antagonists & inhibitors , Triazoles/chemical synthesis , Breast Neoplasms/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Crystallization , Crystallography, X-Ray , Female , Humans , Phosphorylation , Protein-Tyrosine Kinases/metabolism , Receptor, ErbB-2/metabolism , Triazoles/chemistry , Triazoles/pharmacologyABSTRACT
4-Aryl-5-cyano-2H-1,2,3-triazoles bearing a variety of substituting groups on 4-phenyl were synthesized. The chemicals, designed as HER2 tyrosine kinase inhibitors, were screened for bioactivity of inhibiting growth of breast cancer MDA-MB-453 cells. The lowest IC(50) value of inhibiting HER2 tyrosine kinase phosphorylation in breast cancer cells is 6.6microM and the IC(50) value of cell growth inhibition is correspondingly 30.9microM. The lipophilicity of substituting groups on triazoles is the main factor to influence their bioactivities.
Subject(s)
Breast Neoplasms/drug therapy , Cell Proliferation/drug effects , Enzyme Inhibitors/pharmacology , Receptor, ErbB-2/antagonists & inhibitors , Triazoles/chemical synthesis , Breast Neoplasms/metabolism , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Humans , Phosphorylation/drug effects , Triazoles/chemistry , Triazoles/pharmacology , Tumor Cells, Cultured/drug effectsABSTRACT
AIM: To test the enhancing activity and the mechanism of oleyl pyroglutamate used as transdermal enhancer. METHODS: The penetration-enhancing effects of oleyl pyroglutamate, oleyl alcohol and oleic acid on the three drugs (caffeine, tinidazole and cortisone) were observed; the transdermal enhancing mechanism of oleyl pyroglutamate was studied with the attenuated total reflectance Fourier-transfer infrared spectroscopy(ATR-FTIR) of the human stratum corneum in vivo. RESULTS: The penetration-enhancing ratio of the three drugs was 7.9 fold, 41.8 fold and 2.8 fold, respectively. The absorptions at 2,800-2,950 cm-1 and 1,642-1,646 cm-1 (amide-I) in the ATR-FTIR spectrum of the stratum were found to be shifted differently following removal of the stratum corneum which was treated with oleyl pyroglutamate. CONCLUSION: Oleyl pyroglutamate showed better penetration-enhancing effect on the penetration of drugs. Its transdermal enhancing mechanism may be that oleyl pyroglutamate induced not only disordering of the stratum corneum lipid, but also change of the secondary structure of keratin.
