Screening and characterization of estrogenic activity from a hydroxystilbene library

Abstract

The results of this study show that classic olefination chemistry can be adapted to a solid-phase format for parallel synthesis of analog libraries. Although yields varied for the individual analogs, sufficient quantity of pure material was obtained directly from the resin for structural characterization and biological evaluation. This study further validates solid-phase organic synthesis as a useful approach for rapid parallel-manifold library synthesis to augment both lead compound discovery and optimization.

The search for orally active medications through combinatorial chemistry

“…Not surprisingly this involved use of SPOS Horner-Emmons chemistry. 89 Yields ranged from 7-85% and potencies from 5-15 micromolar.…”

Liquid-phase combinatorial synthesis.

“…Peptide libraries secured on solid supports were the first chemically synthesized combinatorial libraries (28)(29)(30)(31). As important as this work was, the need for greater chemical diversity was quickly recognized and an explosion of nonoligomeric heterocyclic libraries has begun to dominate the combinatorial scene (32)(33)(34)(35). An outgrowth of these classes of libraries is the fervent pace to try and adapt solid-phase synthesis to multistep organic reaction sequences.…”

Nonviral gene transfer as a tool for studying transcription regulation of xenobiotic metabolizing enzymes

“…Long duration electroporation allowed higher level expression of GR in mammalian cell lines than standard electro-mediated gene transfer [68]. In addition, a 23-component hydroxystilbene library was screened for estrogenic and anti-estrogenic activity using a cell-based bioassay that measured ER-mediated transcription of a reporter gene using electroporation delivery to ERC1 cells [69]. …”