OPTIMIZING STRUCTURE-BASED VIRTUAL SCREENING PROTOCOL TO IDENTIFY PHYTOCHEMICALS AS CYCLOOXYGENASE-2 INHIBITORS
Abstract: By employing
Databases of Useful Decoys (DUD) and its enhanced version (DUD-E), several
attempts to construct validated Structure-based Virtual Screening (SBVS)
protocols to identify cyclooxygenase-2 (COX-2) inhibitors have been performed.
Both databases tagged active COX-2 inhibitors for compounds with IC50 values
< 1mM. In the search for phytochemicals as natural COX-2 inhibitors,
however, most of their IC50 values are in the micromolar range, which will
likely be identified as non-inhibitors for COX-2 by the available SBVS
protocols. In this article, validation of an SBVS protocol by adding marginal active
COX-2 inhibitors from DUD-E as active compounds is presented. Binary
quantitative-structure activity relationship analysis by using recursive
partition and regression tree method was performed subsequently to optimize the
predictive ability of the protocol. The enrichment factor and the F-measure
values of the optimized protocol could reach 44.78 and 0.47, respectively. The
optimized protocol could identify 1 out of 9 phytochemicals as COX-2
inhibitors.
Author: Enade Perdana
Istyastono
Journal Code: jpfarmasigg160032
