A series of ferrocenyl 1,4 dihydropyridines were synthesized with high yields by a one pot cyclocondensation of formylferrocene,β ketoester and urea(or methyl 3 aminocrotonate) on the surface of SiO 2 under microwave...A series of ferrocenyl 1,4 dihydropyridines were synthesized with high yields by a one pot cyclocondensation of formylferrocene,β ketoester and urea(or methyl 3 aminocrotonate) on the surface of SiO 2 under microwave irradiation without solvent.All products were characterized by EA,IR, and 1 HNMR.展开更多
目的探讨长期使用核苷类似物(NAs)是否导致小鼠肝脏线粒体DNA(mt DNA)ND1和ND4区损伤。方法 7周龄雌性Balb/c小鼠25只,采用简单随机分组法分为5组,对照组和4种核苷类似物组,每组各5只。实验组司他夫定(D4T)50 mg/kg,齐多夫定(AZT)100 mg...目的探讨长期使用核苷类似物(NAs)是否导致小鼠肝脏线粒体DNA(mt DNA)ND1和ND4区损伤。方法 7周龄雌性Balb/c小鼠25只,采用简单随机分组法分为5组,对照组和4种核苷类似物组,每组各5只。实验组司他夫定(D4T)50 mg/kg,齐多夫定(AZT)100 mg/kg,拉米夫定(3TC)50 mg/kg和去羟肌苷(DDI)50 mg/kg,对照组为双蒸水,分别腹腔内注射,每周5次,连续3个月。留取各组肝组织,应用激光捕获显微技术获取肝细胞,对mt DNA ND1和ND4区克隆和测序。结果其余各组肝细胞的mt DNA ND4序列距离与参考序列的平均距离与对照组比较,差异均有高度统计学意义(P<0.01);AZT组肝细胞的mt DNA ND4平均d N与对照组比较,差异有统计学意义(P<0.05);肝细胞mt DNA ND1的序列距离与参考序列的平均距离,AZT组和3TC组序列距离与对照组比较,差异均有统计学意义(P<0.01);DDI组肝组织mt DNA ND1的平均d S与对照组比较,差异有统计学意义(P<0.05);AZT组和3TC组肝细胞mt DNA ND1的平均d S与对照组比较,差异均有统计学意义(P<0.05)。结论长期暴露于NAs可导致小鼠肝细胞mt DNA ND1和ND4区病变。展开更多
Exendin-4 is an incretin mimetic that has been studied as a potent drug for the treatment of the type 2 diabetes. To screen the shorter analogues of Exendin-4 that have the same bioactivity,we designed two analogues o...Exendin-4 is an incretin mimetic that has been studied as a potent drug for the treatment of the type 2 diabetes. To screen the shorter analogues of Exendin-4 that have the same bioactivity,we designed two analogues of Exendin-4: Ex1,deleting this sequence and Ex2,replacing this sequence with three Alas. The proliferation assay of RINm-5F cell using MTT suggested the bioactivity of Ex1 and Ex2 was lower compared to that of Exendin-4 caused by the deletion of LSKQMEEEA. Ex1 and Ex2 had the same strong stability against DPPⅣ with Exendin-4. CD data suggested the helix content of Ex1 had a significant lost,but the helix content of Ex2 was the same as that of Exendin-4. The emission maximum of Ex1 was red-shifted of 3 nm relative to Exendin-4,the absence of this sequence made Trp25 more apt to hydrophilic and the Trp-cage became looser. So we have designed Ex2,the mimetic of Exendin-4 that had the same bioactivity and strong stability against DPPⅣ with Exendin-4 successfully. It became a solid foundation for designing shorter analogues of Exendin-4 for oral drug of diabetes.展开更多
文摘A series of ferrocenyl 1,4 dihydropyridines were synthesized with high yields by a one pot cyclocondensation of formylferrocene,β ketoester and urea(or methyl 3 aminocrotonate) on the surface of SiO 2 under microwave irradiation without solvent.All products were characterized by EA,IR, and 1 HNMR.
文摘目的探讨长期使用核苷类似物(NAs)是否导致小鼠肝脏线粒体DNA(mt DNA)ND1和ND4区损伤。方法 7周龄雌性Balb/c小鼠25只,采用简单随机分组法分为5组,对照组和4种核苷类似物组,每组各5只。实验组司他夫定(D4T)50 mg/kg,齐多夫定(AZT)100 mg/kg,拉米夫定(3TC)50 mg/kg和去羟肌苷(DDI)50 mg/kg,对照组为双蒸水,分别腹腔内注射,每周5次,连续3个月。留取各组肝组织,应用激光捕获显微技术获取肝细胞,对mt DNA ND1和ND4区克隆和测序。结果其余各组肝细胞的mt DNA ND4序列距离与参考序列的平均距离与对照组比较,差异均有高度统计学意义(P<0.01);AZT组肝细胞的mt DNA ND4平均d N与对照组比较,差异有统计学意义(P<0.05);肝细胞mt DNA ND1的序列距离与参考序列的平均距离,AZT组和3TC组序列距离与对照组比较,差异均有统计学意义(P<0.01);DDI组肝组织mt DNA ND1的平均d S与对照组比较,差异有统计学意义(P<0.05);AZT组和3TC组肝细胞mt DNA ND1的平均d S与对照组比较,差异均有统计学意义(P<0.05)。结论长期暴露于NAs可导致小鼠肝细胞mt DNA ND1和ND4区病变。
文摘Exendin-4 is an incretin mimetic that has been studied as a potent drug for the treatment of the type 2 diabetes. To screen the shorter analogues of Exendin-4 that have the same bioactivity,we designed two analogues of Exendin-4: Ex1,deleting this sequence and Ex2,replacing this sequence with three Alas. The proliferation assay of RINm-5F cell using MTT suggested the bioactivity of Ex1 and Ex2 was lower compared to that of Exendin-4 caused by the deletion of LSKQMEEEA. Ex1 and Ex2 had the same strong stability against DPPⅣ with Exendin-4. CD data suggested the helix content of Ex1 had a significant lost,but the helix content of Ex2 was the same as that of Exendin-4. The emission maximum of Ex1 was red-shifted of 3 nm relative to Exendin-4,the absence of this sequence made Trp25 more apt to hydrophilic and the Trp-cage became looser. So we have designed Ex2,the mimetic of Exendin-4 that had the same bioactivity and strong stability against DPPⅣ with Exendin-4 successfully. It became a solid foundation for designing shorter analogues of Exendin-4 for oral drug of diabetes.
