Synthesis, computational studies and enzyme inhibitory kinetics of benzothiazole-linked thioureas as mushroom tyrosinase inhibitors

Herein, we report synthesis of a set of benzothiazole-thiourea hybrids with aromatic and aliphatic side chains (BT1toBT9) using an elegant synthetic strategy. The newly synthesized benzothiazole-thiourea conjugates were subjected to In-vitro tyrosinase inhibition and free radical scavenging activity. Majority of the compounds indicated inhibition considerably improved than the standard; compound (Kojic acid with IC50= 16.8320 +/- 1.1600 mu M)BT2with IC50= 1.3431 +/- 0.0254 mu M was found to be the best inhibitor. A non-competitive mode of inhibition ofBT2was disclosed withKivalue of 2.8 mu M. In order to study enzyme-inhibitor interactions SAR analysis molecular docking was carried out. The amino groups of thiourea were involved in hydrogen bonding with Glu322 showing the bond length of 1.74 and 2.70 angstrom, respectively. Moreover, the coupling of pi-pi was displayed between benzothiazole and benzene rings of His244 and His263, respectively. The outcome of this study might help to develop new inhibitors of melanogenesis, important for cosmetic and food products. Communicated by Ramaswamy H. Sarma

Automated summary

A series of benzothiazole-thiourea hybrids were synthesized, with one compound showing promising inhibition of tyrosinase, potentially useful for developing new inhibitors of melanogenesis.