Identification of novel C-2 symmetric Bis-Azo-Azamethine molecules as competitive inhibitors of mushroom tyrosinase and free radical scavengers: synthesis, kinetics, and molecular docking studies.

Tyrosinase is a multi-copper enzyme found in plants, animals and microorganisms, plays a critical role in the melanogenesis and browning process critical to cosmetics and food industries. Many natural, semi-synthetic and synthetic inhibitors have been discovered. To this end, a small library of symmetrical Bis-Azo-Azamethine hybrids was synthesized and characterized through spectroscopic and analytical data and explored for mushroom tyrosinase and free radical scavenging activity. All of the molecules explicated better potential compared to the standard Kojic acid. On the whole, compound having IC value 0.002 ± 0.004 µM was found to be the most potent derivative. The Kinetic studies were performed for and indicating the mode of inhibition in a competitive manner. Structure Activity Relationship (SAR) analysis and docking studies were carried out. Thus compound bearing bulky naphthyl groups was most potent and, The molecular docking indicated formation of two hydrogen bonds with Arg268 and one hydrophobic interaction with Glu322. The carbonyl oxygen of interacts with Arg268 and form two hydrogen bonds having lengths 2.44 and 2.62 Å, respectively. In the same way, compounds were appraised for DPPH free radical scavenging ability and five of them , , , and were found to exhibit higher % scavenging potency compared with vitamin C, as the standard. Interesting compound was again the most potent in the series. The current investigation points towards the role of naphthyl group in design of new inhibitors of melanogenesis and the antioxidants with improved efficacy.Communicated by Ramaswamy H. Sarma.