A convenient synthesis of 1-alkyl-5-amino-6-phenylethyluracils as potential non-nucleoside HIV-1RT inhibitors

1-Alkyl-5-amino-6-phenylethyluracils （1a, 1b） were synthesized as potential non-nucleoside HIV-1RT inhibitors. A convenient synthetic procedure was developed for the preparation of 1-alkyl-5-amino or 5-aminosubstituted-6-phenylethyluracils, which were synthesized in three or four steps from 6-methyluracil in good yield. The development of a one-pot reaction that simultaneously removed the benzyl protection group and reduced the nitro group greatly improved the yield of the synthesis. Compounds 1a and 1b are analogs of MKC-442, which is an efficient inhibitor of HIV-1 reverse transcriptase, 1a and 1b were tested for their inhibition of HIV-1RT, and moderate activity was found for 1a.

Study on the mechanism of action of Feng-Liao-Chang-Wei-Kang combined with 5-fluorouracil in the treatment of colitis-associated colon cancer

Objective:To investigate the therapeutic effects and mechanisms of Feng-Liao-Chang-Wei-Kang combined with 5-fluorouracil administration in mice with colitis-associated colon cancer.Methods:To establish a colitis-associated colon cancer mouse model and observe the behavior and activity of mice after Feng-Liao-Chang-Wei-Kang and 5-fluorouracil administration;HE staining to observe the pathological changes of mouse colonic tissue;Western blot was used to detect the expression of mouse colon tissue in IL-6/STAT3 pathway-related proteins.Results:The survival rate of mice in the co-administered group was significantly increased,and the intestinal wall thickening and interstitial inflammation of mice were significantly reduced.Western blot results showed that the expression levels of P-STAT3 and IL-6 were significantly increased in the colonic tissue of mice after modeling,and the combined administration inhibited the expression of Cyclin D1,CDK4 and Bcl-2 protein in the IL-6/STAT3 pathway and upregulated the expression of Bax(P<0.05).Conclusion:Feng-Liao-Chang-Wei-Kang combined with 5-fluorouracil inhibits IL-6/STAT3 pathway to exert inhibition of colitis-associated colon cancer inhibition of colitis-associated colon cancer.

Influence of 6-shogaol potentiated on 5-fluorouracil treatment of liver cancer by promoting apoptosis and cell cycle arrest by regulating AKT/mTOR/MRP1 signalling

Currently, chemoresistance seriously attenuates the curative outcome of liver cancer. The purpose of our work was to investigate the influence of 6-shogaol on the inhibition of 5-fluorouracil (5-FU) in liver cancer. The cell viability of cancer cells was determined by MTT assay. Liver cancer cell apoptosis and the cell cycle were examined utilizing flow cytometry. Moreover, qRT–PCR and western blotting was used to analyse the mRNA and protein expression levels, respectively. Immunohistochemistry assays were used to examine multidrug resistance protein 1 (MRP1) expression in tumour tissues. In liver cancer cells, we found that 6-shogaol-5-FU combination treatment inhibited cell viability, facilitated G0/G1 cell cycle arrest, and accelerated apoptosis compared with 6-shogaol or 5-FU treatment alone. In cancer cells cotreated with 6-shogaol and 5-FU, AKT/mTOR pathway- and cell cycle-related protein expression levels were inhibited, and MRP1 expression was downregulated. AKT activation or MRP1 increase reversed the influence of combination treatment on liver cancer cell viability, apoptosis and cell cycle arrest. The inhibition of AKT activation to the anticancer effect of 6-shogaol-5-FU could be reversed by MRP1 silencing. Moreover, our results showed that 6-shogaol-5-FU combination treatment notably inhibited tumour growth in vivo. In summary, our data demonstrated that 6-shogaol contributed to the curative outcome of 5-FU in liver cancer by inhibiting the AKT/mTOR/MRP1 signalling pathway.