Virtual Screening and Molecular Docking Analysis of Degradation Products of Curcumin as Inhibitors of EGFR.

MOLECULAR docking; EPIDERMAL growth factor receptors; CURCUMIN; MOLECULAR dynamics

Epidermal growth factor receptor (EGFR), a member of ErbB family of receptor tyrosine kinases, is reportedly overexpressed in various types of human malignancies. Curcumin, a derived phytochemical compound, has demonstrated antiproliferative effects in various cancer cell lines. Since curcumin degrades into different bioactive compounds, attention has been drawn to analyze if these degradation products are primarily responsible for the observed biological activity of curcumin. In the current work 11 degradation products of curcumin were selected and assessed for their drug likeness, ADME and toxicity properties using a diverse range of advanced computational methods. Binding characteristics of EGFR with these ligand molecules were examined using in silico single ligand molecular docking and multi-ligand simultaneous docking (MLSD) methods. Spiroepoxide, one intermediate product of spontaneous oxidation of curcumin, docked with minimum energy (− 9.123 kcal/mol) as compared to parent curcumin and co-crystallized Erlotinib inhibitor. Vina score for simultaneously docked autooxidation compounds at the binding site of EGFR, where one ligand was curcumin, was lower than the predicted binding energies of singly docked compounds, thus indicating that curcumin-derived compounds produced by the oxidative pathway do take part along with curcumin in inhibiting EGFR. The best 'posed' complex, spiroepoxide bound to EGFR, was chosen for MD simulation to examine the stability of this protein–ligand complex. Eleven degradation products of curcumin were selected and assessed for their drug likeness, ADMET properties, binding characteristics with EGFR using in-silico single ligand molecular docking and (MLSD) multi ligand simultaneous docking methods. The present work finds that Spiroepoxide docks to EGFR in the hydrophobic cavity with the lowest binding score amongst other chosen oxidative metabolites. The binding stability of this docked conformation was confirmed by 50 ns molecular dynamics simulation. [ABSTRACT FROM AUTHOR]

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