Tetrahydroisoquinolines as novel histone deacetylase inhibitors for treatment of cancer

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.

Studying and thinking on clinical research papers published in Chinese Acupuncture & Moxibustion during the last 30 years / 国际中医中药杂志

Objective Through summaring all the randomized controlled trials published in Chinese Acupuncture & Moxibustion during the last 30 years,to investigate clinical researching situation of acupuncture in home and to provide objective and reliable data for other researchers.Methods All clinical research papers published in Chinese Acupuncture & Moxibustion from 1981-2010 was categorized and scored accordingto the size of sample,methods of grouping,and having or not having international or national diagnostic criteria,and then made a comprehensive analysis and comparison.Results ① RCT articles published in Chinese Acupuncture & Moxibustion has increased annually.②The methods of grouping has become more and more normative,which indicates that the level of RCT has been elevated.Of them,randmon digital table has been put into use the most frequently.Conclusion The quality of acupuncture clinical research papers are improving continuously,but the descriptions of the process need to be standardized.

Synthesis and LAR inhibition of 7-alkoxy analogues of illudalic acid / 药学学报

To obtain higher potency and specificity, a series of 7-alkoxy analogues of illudalic acid was synthesized on the base of structure-activity relationship (SAR). All of these compounds exhibited submicromolar inhibition of the enzyme when tested against human leukocyte common antigen-related phosphatase (LAR) (for example, for 15e, IC50 = 180 nmol x L(-1)). They represent the most potent small-molecule inhibitors of LAR so far. These analogues also display excellent selectivity for LAR over other protein tyrosine phosphatases (PTPs) except for the highly homologous PTPsigma. The compound 15f is of 120-fold selectivity for LAR versus PTP-1B inhibition. The development of potent enzyme-specific inhibitors is so important that they may serve both as tools to study the role of LAR and as therapeutic agents for treatment of type II diabetes.