Synthesis of 7200 small molecules based on a substructural analysis of the histone deacetylase inhibitors trichostatin and trapoxin.

نویسندگان

  • S M Sternson
  • J C Wong
  • C M Grozinger
  • S L Schreiber
چکیده

Seventy-two hundred potential inhibitors of the histone deacetylase (HDAC) enzyme family, based on a 1,3-dioxane diversity structure, were synthesized on polystyrene macrobeads. The compounds were arrayed for biological assays in a "one bead-one stock solution" format. Metal-chelating functional groups were used to direct the 1,3-dioxanes to HDAC enzymes, which are zinc hydrolases. Representative structures from this library were tested for inhibitory activity and the 1,3-dioxane structure was shown to be compatible with HDAC inhibition. [structure: see text]

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Effect of trichostatin A on histone deacetylase 1 (HDAC 1) and CIP/KIP (p21CIP1/WAF1, p27KIP1, and p57KIP2) gene expression, cell growth inhibition and apoptosis induction in lung cancer COR-L105 cell line. Abstract

Effect of trichostatin A on histone deacetylase 1 (HDAC 1) and CIP/KIP (p21CIP1/WAF1, p27KIP1, and p57KIP2) gene expression, cell growth inhibition and apoptosis induction in lung cancer COR-L105 cell line. Abstract Background: Lung cancer is one the leading cause of cancer-related death worldwide, with more than 1.2 million deaths each year. In addition to genetic mutations, epigenetic modif...

متن کامل

Search for the Pharmacophore of Histone Deacetylase Inhibitors Using Pharmacophore Query and Docking Study

Histone deacetylase inhibitors have gained a great deal of attention recently for the treatment of cancers and inflammatory diseases. So design of new inhibitors is of great importance in pharmaceutical industries and labs. Creating pharmacophor models in order to design new molecules or search a library for finding lead compounds is of great interest. This approach reduces the overall cost ass...

متن کامل

Search for the Pharmacophore of Histone Deacetylase Inhibitors Using Pharmacophore Query and Docking Study

Histone deacetylase inhibitors have gained a great deal of attention recently for the treatment of cancers and inflammatory diseases. So design of new inhibitors is of great importance in pharmaceutical industries and labs. Creating pharmacophor models in order to design new molecules or search a library for finding lead compounds is of great interest. This approach reduces the overall cost ass...

متن کامل

Depudecin induces morphological reversion of transformed fibroblasts via the inhibition of histone deacetylase.

Depudecin is a fungal metabolite that reverts the rounded phenotype of NIH 3T3 fibroblasts transformed with v-ras and v-src oncogenes to the flattened phenotype of the nontransformed parental cells. The mechanism of detransformation induced by this agent had not been determined. Here, we demonstrate that depudecin inhibits histone deacetylase (HDAC) activity effectively both in vivo and in vitr...

متن کامل

RED CELLS Induction of human globin gene expression by histone deacetylase inhibitors

We investigated the induction of human globin gene activity by 3 classes of histone deacetylase inhibitors: amide analogues of trichostatin A, hydroxamic acid analogues of trapoxin, and scriptaid and its analogues. The screening consisted of measuring the effects of these compounds on and human gene promoter activity by using cultures of GM979 cells stably transfected with a construct containin...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Organic letters

دوره 3 26  شماره 

صفحات  -

تاریخ انتشار 2001