Pharmacophore modeling and virtual screening for the discovery of new type 4 cAMP phosphodiesterase (PDE4) inhibitors.

ABSTRACT: Type 4 cAMP phosphodiesterase (PDE4) inhibitors show a broad spectrum of anti-inflammatory effects in almost all kinds of inflamed cells, by an increase in cAMP levels which is a pivotal second messenger responsible for various biological processes. These inhibitors are now considered as the potential drugs for treatment of chronic inflammatory diseases. However, some recently marketed inhibitors e.g., roflumilast, have shown adverse effects such as nausea and emesis, thus restricting its use. In order to identify novel PDE4 inhibitors with improved therapeutic indexes, a highly correlating (r = 0.963930) pharmacophore model (Hypo1) was established on the basis of known PDE4 inhibitors. Validated Hypo1 was used in database screening to identify chemical with required pharmacophoric feature

SUBMITTER: Niu M 

PROVIDER: S-EPMC3858292 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature