Organocatalyzed and mechanochemical solvent-free synthesis of novel and functionalized bis-biphenyl substituted thiazolidinones as potent tyrosinase inhibitors: SAR and molecular modeling studies

Eluding the involvement of solvents in organic synthesis and introducing environment friendly procedures can control environmental problems. A facile and an efficient solvent free mechanochemical method (grinding) is achieved to synthesize novel bis-biphenyl substituted thiazolidinones using nontoxic and cheap N-acetyl glycine (NAG). Organocatalytic condensation of a series of Schiff's bases bearing different substituents with thioglycolic acid produces a variety of thiazolidinones derivatives in good to excellent yield. In vitro inhibition studies against mushroom tyrosinase of these thiazolidinone analogues revealed that many of them possessed good to excellent tyrosinase inhibition at low micro molar concentrations. In particular, six compounds exhibited potent inhibitory potential with IC50 values ranging from 0.61 +/- 0.31 to 21.61 +/- 0.11 mu M as compared with that of standard kojic acid (IC50 6.04 +/- 0.11 M). Further molecular docking studies revealed that the thiazolidinones moiety plays a key role in the inhibition mechanism by well fitting into the enzyme bounding pocket. (C) 2017 Elsevier Masson SAS. All rights reserved.