NFκβ INHIBITION MECHANISM OF DEOXYELEPHANTOPIN AND ISODEOXYELE-PHANTOPIN WITH QSAR AND MOLECULAR DOCKINGAbstract
Deoxyelephantopin and isodeoxyelephantopin are member of a group of compounds, sesquiterpene lactones, that include proven anticancer agents against many types of cancer cells. Many sesquiterpene lactones suppress cancers by inhibiting NFκβ. This study explores the inhibitory interaction between deoxyelephantopin and isodeoxyelephantopin on NFκB using QSAR and molecular docking. Physicochemical properties and NFκβ (pIC50) inhibition values of a number of sesquiterpene lactone compounds from in–vitro studies were used as reference data in constructing the QSAR model equation. This model was used to predict the inhibition potential of deoxyelephantopin and isodeoxyelephantopin on NFκβ. This result was confirmed with molecular docking. The potential NFκβ inhibition of deoxyelephantopin and isodeoxyelephantopin obtained were 59.1037 μM and 62.0321 μM, respectively, with RMSE = 0.07831 R2 = 0.95465 and Q2 = 0.67719. Both test compounds showed affinity for the Lys 122 receptor residue (PDB ID: 1NF1) with a docking score of -9.5318 kcal/mol and -8.4429 kcal/mol, respectively.
Frengki *, D. P. Putra, F. Sriwahyuni, D. Khambri and H. Vanda
Department of Biomedicine, Faculty of Medicine, Andalas University, Padang, West Sumatera, Indonesia.
11 October 2018
10 March 2019
16 March 2019
01 July 2019