Advances in antidepressants based on the regulation of serotonin receptors / 中国药科大学学报

@#The etiology and pathogenesis of depression is complex, the regulation of serotonin signaling pathway is one of the most important mechanisms for commercially available antidepressants. In addition to serotonin transporter, recent studies have shown many other serotonin receptor subtypes also play an important role in the treatment of depression, which has become one of the hot topics of antidepressants. Therefore, the progress of serotonin receptors and new structure with the activity of regulating serotonin receptors as well as part of the structure-activity relationships are reviewed in this paper in order to provide reference for the further research and development of antidepressants.

Synthesis and xanthine oxidase inhibitory activities of 2-phenyl-tetrahydrothiopyrano［4, 3-d］ pyrimidine derivatives / 中国药科大学学报

@#Twelve novel 2-phenyl -tetrahydrothiopyrano［4, 3-d］pyrimidine derivatives were synthesized from 4-hydroxy-benzonitrile by etherification, hydrolysis, acylation and addition reactions, etc. The inhibitory activities against xanthine oxidase were evaluated in vitro. Results showed that compounds 8a-8h exhibited varying inhibitory potencies on xanthine oxidase at 100 μmol/L, significantly better than those of compounds 6a-6d, indicating that carboxy-substituted pyrimidine is beneficial to the inhibitory activity. Among compounds 8a-8h, 8f with isopropionic acid-substituted pyrimidine and ethyl-substituted phenol showed the best inhibition with IC50 of 76. 0 μmol/L.

Small interfering RNA mediated silencing of cytochrome P450 3A4 gene / 中国基层医药

Objective To investigate the inhibitory effect of the cytochrome P450 3A4(CYP3A4) gene expression and function in CHL-3A4 cells lines by vector-ecpressed small hairpin interfering RNA(shRNA).Methods The shRNA expression vectors targeting CYP 3A4 gene(CYP3A4Ⅰ,CYP3A4Ⅱ,CYP3A4Ⅲ) were designed and constructed.The inhibitory effect of shRNA was detected by Western blot and RT-PCR analysis.The inhibitory effect of cytotoxic of cyclophosphamide using shRNA was measured by MTT assay.Results CYP3A4Ⅲ shRNA expressing vector significantly reduced the CYP3A4 mRNA(70%) and protein expression levels(75%) of the CYP3A4 gene in CHL3A4 cells suppression of CYP3A4 gene expression by CYP3A4Ⅲ largely reversed cyclophosphamide cytotoxicity(75%) in CHL-3A4 cells.Conclusion Vector-based RNAi could suppress CYP3A4 gene expression and function,and the use of RNAi to inhibit CYP3A4 gene expression in mammalian cells was a promising new tool for the study of cytochrome P450 gene function.

Caco-2 cell model——an effective tool for the research of drug absorption / 中国药理学通报

The absorption process is an important factor in determining the bioavailability of orally administered drugs. however, the absorption mechanism of many drugs is not clear. Caco-2 cell model is the best in vitro absorption model nowadays. It is widely used in the research on drug absorption process and absorption mechanism, especially in the aspect of traditional Chinese medicine absorption, the use of Caco-2 cell model has become the hot spot recently. Mo- reover, Caco-2 cell model is also applied in the research on drug metabolism. Therefore, Caco-2 cell model will become an important method in the research of drug absorption, and will be helpful to accelerate the process of new drug screening and development.