A series of spirooxindole-ferrocene hybrids bearing five or four contiguous chiral centers were designed and synthesized via organocatalysis.In vitro protein binding and cellular proliferation assays suggested that co...A series of spirooxindole-ferrocene hybrids bearing five or four contiguous chiral centers were designed and synthesized via organocatalysis.In vitro protein binding and cellular proliferation assays suggested that compound 5 d was the most potent mouse double minute 2 homolog(MDM2)inhibitor.In addition,mechanistic studies indicated that compound 5 d suppressed MDM2-mediated p53 degradation,induced apoptosis and promoted oxidative damage.Molecular docking studies have suggested that 5 d binds to MDM2 by mimicking the Trp23 and Leu26 residues of p53.This work can provide a basis for the development of novel multifunctional MDM2 inhibitors.The further exploration of more derivatives from this library and additional investigation of organocatalysis application in the development of new molecules may generate new potential lead compounds for cancer-targeted therapy.展开更多
In this paper,we examine how bond rating downgrades affect common stock prices in China by using the data of all the bond rating downgrades in China during the period from 1 January 2008 to 30 May 2016.To provide empi...In this paper,we examine how bond rating downgrades affect common stock prices in China by using the data of all the bond rating downgrades in China during the period from 1 January 2008 to 30 May 2016.To provide empirical evidence for the theory in Goh and Ederington(1993),we classify the samples according to the downgrade reasons and the bonds’time to maturity and examine the abnormal returns of each group in different windows.The empirical results show that the downgrades due to deteriorating financial prospects have a negative effect on stock prices and that this effect lags behind.The downgrades due to leverage changes have no significant effect on stock prices.Meanwhile,the variation in the decrease in stock prices due to rating downgrades of bonds that will mature within three years is significantly larger than that of those which will mature after more than three years.展开更多
基金supported by grants from the National Natural Science Foundation(Nos.21772131,81672552,81773890,82073997)the Fundamental Research Funds of Science&Technology Department of Sichuan Province(Nos.2019YFSY0004,2017JY0226,2019YFS0298)Project First-Class Disciplines Development supported by CDUTCM。
文摘A series of spirooxindole-ferrocene hybrids bearing five or four contiguous chiral centers were designed and synthesized via organocatalysis.In vitro protein binding and cellular proliferation assays suggested that compound 5 d was the most potent mouse double minute 2 homolog(MDM2)inhibitor.In addition,mechanistic studies indicated that compound 5 d suppressed MDM2-mediated p53 degradation,induced apoptosis and promoted oxidative damage.Molecular docking studies have suggested that 5 d binds to MDM2 by mimicking the Trp23 and Leu26 residues of p53.This work can provide a basis for the development of novel multifunctional MDM2 inhibitors.The further exploration of more derivatives from this library and additional investigation of organocatalysis application in the development of new molecules may generate new potential lead compounds for cancer-targeted therapy.
基金This research was supported by the National Natural Science Foundation of China[Grant Nos.71703162 and 71501178].
文摘In this paper,we examine how bond rating downgrades affect common stock prices in China by using the data of all the bond rating downgrades in China during the period from 1 January 2008 to 30 May 2016.To provide empirical evidence for the theory in Goh and Ederington(1993),we classify the samples according to the downgrade reasons and the bonds’time to maturity and examine the abnormal returns of each group in different windows.The empirical results show that the downgrades due to deteriorating financial prospects have a negative effect on stock prices and that this effect lags behind.The downgrades due to leverage changes have no significant effect on stock prices.Meanwhile,the variation in the decrease in stock prices due to rating downgrades of bonds that will mature within three years is significantly larger than that of those which will mature after more than three years.
