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

The present study describes the anti-melanogenesis effect of Acemetacin (ACE). Essentialprotein (melanin) that is vital for the skin for defense from UV rays. In the present research,emerging drugACE was examined for its melanin inhibition using three different (in vitro, in vivoand computational) methods. ACE showed remarkable potency (IC50= 0.353 ± 0.003 μM) againsttyrosinase in the comparison of standard, kojic acid (IC50= 16.841 ± 1.161 μM) and ACEexhibited competitive inhibition. In thein vivostudy 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, ACEexpressively (P<0.001) reduced the level of pigmentation (62.89%) ata concentration of 20 μM,relative to that of kojic acid (39.64%). The binding profile of ACE was confirmed by moleculardocking and the stability of the docked complexes was justified by MD simulation. Based on ourresults, it was concluded that ACE possessed good therapeutic potential against melanogenesis bytargeting the tyrosinase.