Computer aided drug design: Pharmacophore, QSAR and docking studies for novel anti-inflammatory natural compounds

Bezofuran-type neolignan, is a group of natural compounds, bearing diverse bioactivity, especially anti-inflammation, and anti-cancer. We had synthesized a set of 39 benzo-fused analogs which gave significant activities on inhibition against NF-KB receptor. Hence, this study aims to apply a computer-aided drug design to establish models as a virtual screening method to find potent natural benzofuran neolignans for anti-inflammatory via inhibiting NF-KB. Using Molecular Operation Environment (MOE) software version 2015.10, a QSAR model was built using 6 two-dimensional molecular descriptors that gave acceptable predictive ability (
$R^{2}= 0.8172, R^{2}_{-}test= 0.7606, R_{cv}^{2}= 0.63609, RMSE = 0.14748$
). The model highlighted that logP(o/w) values considerably contributed to the inhibition of NF-KB. The 3D-pharmacophore model showed 3 features: 2 aromatic centroids and 1 hydrophobic centroid which are nearly planar (157.9 degrees). The virtual screening on 118 natural benzofuran neolignans showed 9 hit compounds with binding energy less than -6.0 kcal have predicted activity smaller than 0.1-fold action. These 9 final compounds: A. 7, A.15, A.16, A.21, A.29, A.54, A.55, A. 76, and A.98 would be models for drug design and potential for further in vitro and in vivo studies.