In Vitro and In Silico Study of 5-[(4-Methylpiperazin-1-yl) methyl]dehydrozingerone and 5-(Morpholin-4-ylmethyl) dehydrozingerone as Lipoxygenase and Xanthine Oxidase Inhibitor

Abstract

The present study was to evaluate the two aminomethyl derivatives of dehydrozingerone: 5-[(4-methylpiperazin-1-yl)methyl]dehydrozingerone and 5-(morpholin-4-ylmethyl)dehydrozingerone as lipoxygenase and xanthine oxidase inhibitors. Nordihydroguaiaretic acid, allopurinol and the parent compound dehydrozingerone were used as comparative compounds. Results indicated that 5-[(4-methylpiperazin-1-yl)methyl] dehydrozingerone and 5-(morpholin-4-ylmethyl) dehydrozingerone inhibited the lipoxygenase enzyme with half-maximal inhibitory concentration of 219.13 and 269.39 μM, respectively. Their activities were comparable to nordihydroguaiaretic acid with a half-maximal inhibitory concentration of 216.84 μM. The compounds were also found to inhibit the xanthine oxidase enzyme with half-maximal inhibitory concentration of 102.34 and 230.52 μM, respectively, but their activities were lower than allopurinol with half-maximal inhibitory concentration of 34.09 μM. Dehydrozingerone was found inactive both as a lipoxygenase inhibitor and xanthine oxidase inhibitor. Besides, in silico study was carried out to predict the binding interaction between the enzymes and the compounds compared to each of positive controls. In conclusion, 5-[(4-methylpiperazin-1-yl)methyl] dehydrozingerone has lipoxygenase inhibitory activity comparable to nordihydroguaiaretic acid, but they have lower xanthine oxidase inhibitory activity than allopurinol.