Docking studies of artemether and curcumin with pro-inflammatory inhibitory proteins and their in-vivo simulation on level of lysosomal acid hydrolyses

Abstract

Context: The present work is to perform a docking analysis by AutoDock version 4.2 for artemether (ARM) and curcumin (CUR) with few validated protein targets (cyclooxygenase [COX-2] and tumor necrosis factor [TNF-α]) for anticancer therapy. Aims: The object of this work was to analyze inhibitory action of one artemisinin derivative ARM and a natural coloring pigment CUR against pro-inflammatory (a chemical substance that became inflammatory only after it is altered by metabolic process) by computational docking parameters and simulate these effects on the adjuvant arthritic rats were compared with that of drug combination and indomethacin. Materials and Methods: Two-dimensional (2-D) Structure of ARM and CUR was drawn using ChemSketch, the 2-D structure of ligands as well as receptor were converted into the three-dimensional (3-D) structure and optimized with 3-D geometry. The regions of interest used by AUTODOCK version 4.2 were defined by considering grid area by making a grid box around the active sites. The anti-inflammatory activity of ARM and CUR was assessed by measuring paws swelling and lysosomal enzyme activity in control and experimental rates. Results: The binding energy of the ARM and CUR with the human COX and TNF-α protein is found accordingly. That is the indication of two molecular combinations and their efficacy explain against the pro-inflammatory protein scaffolds. Increased paw diameter and lysosomal enzyme activity in the arthritic animals were significantly suppressed to near normal levels in rats treated with an equimolar concentration of drug combination and 3 mg/kg indomethacin. Conclusions: A good correlation was observed in binding affinity of ARM and CUR against the selected targets for pro-inflammatory enzyme inhibition. These results indicate that combination of the drug has promising anti-arthritic activity as a result of its stabilizing action on lysosomal enzyme activity.