Abstract

STRUCTURE-BASED DESIGN OF CURCUMIN ANALOGS AS POTENTIAL EGFR AND XANTHINE OXIDASE INHIBITORS: A COMPUTATIONAL APPROACH

Narsaiah Chelimela, Shobha Rani Satla*

Abstract

Therapy against cancer prevention currently revolves around the use of plant-derived anticancer drugs. In this regard, Curcumin underlines a high potential as an anticancer drug with a high affinity toward different drug targets explored in the pathophysiology of cancer. To counteract the pharmacokinetic insufficiencies of curcumin, a library of triferuloyl methane analogs were designed using computational tools. Initially, a target search was carried out for these derivatives and the most relevant ones were selected for molecular docking. Molecular docking identified hit molecules 22 and 902 against EGFR2, and 890 and 902 against Xanthine oxidase with significantly higher docking scores than cocrystallized ligands. The obtained docked complexes were subjected to MD simulations for 100s. Determination of all the relevant parameters revealed the ability of these hit molecules against these drug targets. Furthermore, MM-GBSA studies evaluated the binding free energies of the complexes, thereby corroborating the potential of the hit molecules to bind with these targets.

Keywords: EGFR2, Xanthine oxidase, Molecular docking, Molecular dynamics, MMGBSA.