Histone acetylation is a critical process in the regulation of chromatin structure and gene expression.Histone deacetylases(HDACs)remove the acetyl group,leading to chromatin condensation and transcriptional repressio...Histone acetylation is a critical process in the regulation of chromatin structure and gene expression.Histone deacetylases(HDACs)remove the acetyl group,leading to chromatin condensation and transcriptional repression.HDAC inhibitors are considered a new class of anticancer agents and have been shown to alter gene transcription and exert antitumor effects.This paper describes our work on the structural determination and structure-activity relationship(SAR)optimization of tetrahydroisoquinoline compounds as HDAC inhibitors.These compounds were tested for their ability to inhibit HDAC 1,3,6 and for their ability to inhibit the proliferation of a panel of cancer cell lines.Among these,compound 82 showed the greatest inhibitory activity toward HDAC 1,3,6 and strongly inhibited growth of the cancer cell lines,with results clearly superior to those of the reference compound,vorinostat(SAHA).Compound 82 increased the acetylation of histones H3,H4 and tubulin in a concentration-dependent manner,suggesting that it is a broad inhibitor of HDACs.展开更多
The in vitro oxidative hemolysis of human red blood cells (RBC) was used as a model to study the free radical induced damage of biological membranes and the inhibitory effect of natural antioxidants. The hemolysis was...The in vitro oxidative hemolysis of human red blood cells (RBC) was used as a model to study the free radical induced damage of biological membranes and the inhibitory effect of natural antioxidants. The hemolysis was induced by a water-soluble free radical initiator 2,2’-azo(2-asmidinopropane)dihydrochloride (AAPH) and inhibited by the principal polyphenolic components extracted from green tea leaves, i.e. (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicat-echin gallate (ECG), (-)-epigallocatechin gallate (EGCG) and gallic acid (GA). Addition of AAPH at 37℃ caused fast hemolysis after a short period of inhibition period, while addition of the green tea polyphenols efficiently suppressed the hemolysis in the activity sequence of EGCG 】 EGC】 ECG ≈EC】GA, demonstrating that these green tea polyphenols are effective antioxidants which could protect biological membranes from free radical induced oxidative damage.展开更多
基金supported financially by the National Science & Technology Major Project ‘Key New Drug Creation and Manufacturing Program’ of China(Grant No.2014ZX09507002)the National Marine ‘863’ Project(No.2013AA092902)
文摘Histone acetylation is a critical process in the regulation of chromatin structure and gene expression.Histone deacetylases(HDACs)remove the acetyl group,leading to chromatin condensation and transcriptional repression.HDAC inhibitors are considered a new class of anticancer agents and have been shown to alter gene transcription and exert antitumor effects.This paper describes our work on the structural determination and structure-activity relationship(SAR)optimization of tetrahydroisoquinoline compounds as HDAC inhibitors.These compounds were tested for their ability to inhibit HDAC 1,3,6 and for their ability to inhibit the proliferation of a panel of cancer cell lines.Among these,compound 82 showed the greatest inhibitory activity toward HDAC 1,3,6 and strongly inhibited growth of the cancer cell lines,with results clearly superior to those of the reference compound,vorinostat(SAHA).Compound 82 increased the acetylation of histones H3,H4 and tubulin in a concentration-dependent manner,suggesting that it is a broad inhibitor of HDACs.
文摘The in vitro oxidative hemolysis of human red blood cells (RBC) was used as a model to study the free radical induced damage of biological membranes and the inhibitory effect of natural antioxidants. The hemolysis was induced by a water-soluble free radical initiator 2,2’-azo(2-asmidinopropane)dihydrochloride (AAPH) and inhibited by the principal polyphenolic components extracted from green tea leaves, i.e. (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicat-echin gallate (ECG), (-)-epigallocatechin gallate (EGCG) and gallic acid (GA). Addition of AAPH at 37℃ caused fast hemolysis after a short period of inhibition period, while addition of the green tea polyphenols efficiently suppressed the hemolysis in the activity sequence of EGCG 】 EGC】 ECG ≈EC】GA, demonstrating that these green tea polyphenols are effective antioxidants which could protect biological membranes from free radical induced oxidative damage.
