Azido-3′-deoxythymidine(AZT) was the first clinically approved drug against HIV infection, despite its undesirable side reactions, such as bone marrow suppression. In our aim to develop new chemical entity of anti-tu...Azido-3′-deoxythymidine(AZT) was the first clinically approved drug against HIV infection, despite its undesirable side reactions, such as bone marrow suppression. In our aim to develop new chemical entity of anti-tumor and anti-HIV, the H-phosphonate 6 of AZT conjugate with diosgenin was synthesized by a tandem transesterification reaction for the first time. There are the merits of easy operation and high yield in the reported method. It could be extended to synthesize other diosgenin phosphonate conjugates such as carbohydrate and peptide.展开更多
To investigate the synergistic effects of 3′-azido-3′- deoxythymidine （AZT） and FA-2-b-β extracted from Ling Jin mushroom on apoptosis of gastric cancer cells MKN45 in vitro. METHODS： Ml-I- analysis was made to ...To investigate the synergistic effects of 3′-azido-3′- deoxythymidine （AZT） and FA-2-b-β extracted from Ling Jin mushroom on apoptosis of gastric cancer cells MKN45 in vitro. METHODS： Ml-I- analysis was made to examine the inhibition rate of MKN45 cells treated with AZT （2.5, 5, 10 and 20 mg/L） and FA-2-b-13 （5, 10, 20 and 40 mg/L） singly and combinatively for 24, 48 and 72 h. Apoptotic effects were evaluated by morphological methods, DNA agarose gel electrophoresis and flow cytometry, respectively. Telomerase activity was estimated by TRAP- ELISA. The mRNA expression of caspase-3 and Bcl-2 were detected by RT-PCR. RESULTS： AZT and FA-2-b-13 could significantly inhibit MKN45 cell proliferation and induce its apoptosis. MKN45 cells were inhibited in dose- and time- dependent manner. The inhibition effect of AZT combined with FA-2- b-β was obviously better than that used singly （0.469 ＋ 0.022 vs 1.075 4- 0.055, P 〈 0.05, 0.325 4- 0.029 vs 0.469 ＋ 0.022 P 〈 0.01）. AZT used singly and combination of FA-2-b-β could decrease the activity of tumor cell telomerase, and AZT has synergistic function with FA- 2-b-β. A certain concentration of AZT could up-regulate the expression of caspase-3 mRNA （r = 0.9969, P 〈 0.01）, which was positively related to apoptosis rate, and could down-regulate the expression of Bcl-2 mRNA, which was negatively related to apoptosis rate （r = 0.926, P 〈 0.01）. Furthermore, the effect of AZT combined with FA-2-b-13 was significantly higher than that used singly. CONCLUSION： Combination of AZT and FA-2-b-β has an obviously synergetic effect in the gastric cancer cells MKN45, which has provided a new approach to the treatment of gastric cancer clinically.展开更多
The assays for bovine immunodeficiency virus (BIV) induced syncytium formation and BIV long terminal repeat (LTR) directed luciferase (Luc) gene expression were applied to screen and evaluate anti AIDS drugs. Frequen...The assays for bovine immunodeficiency virus (BIV) induced syncytium formation and BIV long terminal repeat (LTR) directed luciferase (Luc) gene expression were applied to screen and evaluate anti AIDS drugs. Frequency of the syncytium formation and BIV LTR directed Luc activity were in proportion to the number of input BIV infected cells. AZT inhibited the syncytium formation and the BIV LTR directed Luc gene expression level. Its inhibitory effects were dosedependent with the IC 50 being 0.24 and 0.052 mmol / L, respectively.展开更多
文摘Azido-3′-deoxythymidine(AZT) was the first clinically approved drug against HIV infection, despite its undesirable side reactions, such as bone marrow suppression. In our aim to develop new chemical entity of anti-tumor and anti-HIV, the H-phosphonate 6 of AZT conjugate with diosgenin was synthesized by a tandem transesterification reaction for the first time. There are the merits of easy operation and high yield in the reported method. It could be extended to synthesize other diosgenin phosphonate conjugates such as carbohydrate and peptide.
文摘To investigate the synergistic effects of 3′-azido-3′- deoxythymidine （AZT） and FA-2-b-β extracted from Ling Jin mushroom on apoptosis of gastric cancer cells MKN45 in vitro. METHODS： Ml-I- analysis was made to examine the inhibition rate of MKN45 cells treated with AZT （2.5, 5, 10 and 20 mg/L） and FA-2-b-13 （5, 10, 20 and 40 mg/L） singly and combinatively for 24, 48 and 72 h. Apoptotic effects were evaluated by morphological methods, DNA agarose gel electrophoresis and flow cytometry, respectively. Telomerase activity was estimated by TRAP- ELISA. The mRNA expression of caspase-3 and Bcl-2 were detected by RT-PCR. RESULTS： AZT and FA-2-b-13 could significantly inhibit MKN45 cell proliferation and induce its apoptosis. MKN45 cells were inhibited in dose- and time- dependent manner. The inhibition effect of AZT combined with FA-2- b-β was obviously better than that used singly （0.469 ＋ 0.022 vs 1.075 4- 0.055, P 〈 0.05, 0.325 4- 0.029 vs 0.469 ＋ 0.022 P 〈 0.01）. AZT used singly and combination of FA-2-b-β could decrease the activity of tumor cell telomerase, and AZT has synergistic function with FA- 2-b-β. A certain concentration of AZT could up-regulate the expression of caspase-3 mRNA （r = 0.9969, P 〈 0.01）, which was positively related to apoptosis rate, and could down-regulate the expression of Bcl-2 mRNA, which was negatively related to apoptosis rate （r = 0.926, P 〈 0.01）. Furthermore, the effect of AZT combined with FA-2-b-13 was significantly higher than that used singly. CONCLUSION： Combination of AZT and FA-2-b-β has an obviously synergetic effect in the gastric cancer cells MKN45, which has provided a new approach to the treatment of gastric cancer clinically.
文摘The assays for bovine immunodeficiency virus (BIV) induced syncytium formation and BIV long terminal repeat (LTR) directed luciferase (Luc) gene expression were applied to screen and evaluate anti AIDS drugs. Frequency of the syncytium formation and BIV LTR directed Luc activity were in proportion to the number of input BIV infected cells. AZT inhibited the syncytium formation and the BIV LTR directed Luc gene expression level. Its inhibitory effects were dosedependent with the IC 50 being 0.24 and 0.052 mmol / L, respectively.
