Binary Quantitative Structure-Activity Relationship Analysis to Increase the Predictive Ability of Structure-Based Virtual Screening Campaigns Targeting Cyclooxygenase-2

Abstract

Structure-Based Virtual Screening (SBVS) campaigns employing Protein-Ligand Interaction Fingerprints (PLIF) identification have served as a powerful strategy in fragments and

Virtual Screening Campaigns on Isoflavones to Discover Potent Cyclooxygenase-2 Inhibitors

“…Only compounds with isoflavone substructure (Figure 1) were selected. The compounds were downloaded in the SMILE formats and subsequently subjected to SBVS protocol to identify potent COX-2 inhibitors developed by Istyastono (2017).…”

“…Similar to Istyastono (2017), all computation were performed on a Linux (Ubuntu 10.04 LTS Lucid Lynx) machine with Intel(R) Xeon(R) CPU E3-1220 as the processors (Quad-Core @ 3.10 GHz) and 8.00 GB of RAM. The applications employed in this research were SPORES (ten Brink and Exner, 2009), PLANTS1.2 (Korb et al, 2009(Korb et al, , 2007, Open Babel 2.2.3 (O'Boyle et al, 2011), and PyPLIF 0.1.1 (Radifar et al, 2013b).…”

“…Computational medicinal chemistry tools especially structure-based virtual screening (SBVS) campaigns have become a routine of work in drug discovery (Chen, 2015;Weiss et al, 2016). Recently, an SBVS protocol to identify potent cyclooxygenase-2 has just published (Istyastono, 2017). The protocol uses PLANT1.2 docking software (Korb et al, 2009(Korb et al, , 2007, PyPLIF (Radifar et al, 2013a(Radifar et al, , 2013b, and the best decision tree resulted from binary quantitative structureactivity analysis of the results in retrospective validation using DUD-E (Mysinger et al, 2012).…”

“…The protocol uses PLANT1.2 docking software (Korb et al, 2009(Korb et al, , 2007, PyPLIF (Radifar et al, 2013a(Radifar et al, , 2013b, and the best decision tree resulted from binary quantitative structureactivity analysis of the results in retrospective validation using DUD-E (Mysinger et al, 2012). Compared to previously published SBVS protocols (Huang et al, 2006;Istyastono, 2016;Krüger and Evers, 2010;Mysinger et al, 2012;Yuniarti et al, 2011), this protocol shows better predictive ability with enrichment factor (EF) value of 273.166 (Istyastono, 2017). The SBVS protocol with substantially better predictive ability offers opportunities to efficiently discover novel inhibitors for cyclooxygenase-2 (COX-2).…”

“…The research presented in this article aimed to discover isoflavones as novel potent COX-2 inhibitors. The SBVS protocol constructed and retrospectively validated by Istyastono (2017) to identify potent COX-2 inhibitors were employed to virtually screen isoflavones collected in the ZINC15 database (Sterling and Irwin, 2015). Three isoflavones were identified in the research presented in this article.…”