Exploration of Mechanistic Insights of Acemetacin in Melanogenesis Through Zebrafish Model, Enzyme Kinetics, Molecular Docking and Simulation Approaches

Abstract

The present study describes the anti‐melanogenesis effect of Acemetacin (ACE). Essential protein (melanin) that is vital for the skin for defense from UV rays. In the present research, emerging drug ACE was examined for its melanin inhibition using three different (in vitro, in vivo and computational) methods. ACE showed remarkable potency (IC50 = 0.353 ± 0.003 µM) against tyrosinase in the comparison of standard, kojic acid (IC50 = 16.841 ± 1.161 µM) and ACE exhibited competitive inhibition. In the in vivo study zebrafish embryos were exposed with 5, 10, 15 and 20 µM of ACE and same doses for positive control (Kojic Acid). At 72 h treatment, ACE expressively (P<0.001) reduced the level of pigmentation (62.89%) at a concentration of 20 µM, relative to that of kojic acid (39.64%). The binding profile of ACE was confirmed by molecular docking and the stability of the docked complexes was justified by MD simulation. Based on our results, it was concluded that ACE possessed good therapeutic potential against melanogenesis by targeting the tyrosinase.

Keywords

• acemetacin
• tyrosinase inhibition
• melanogenesis
• computational studies