Oxazolones: New tyrosinase inhibitors; synthesis and their structure-activity relationships

The tyrosinase inhibitory potential of seventeen synthesized oxazolone derivatives has been evaluated and their structure-activity relationships developed in the present work. All the synthesized derivatives, 3-19, demonstrated excellent in vitro tyrosinase inhibitory properties having IC50 values in the range of 1.23 +/- 0.37-17.73 +/- 2.69 mu M, whereas standard inhibitors L-mimosine and kojic acid have IC50 values 3.68 +/- 0.02 and 16.67 +/- 0.52 mu M,, respectively. Compounds 4-8 having IC50 values 3.11 +/- 0.95, 3.51 +/- 0.25, 3.23 +/- 0.66, 1.23 +/- 0.37, and 2.15 +/- 0.75, respectively, were found to be very active members of the series, even better than both the standard inhibitors. However, compounds 3, 9-11, 13, 14, 16, 17, and 19 were found to be better than kojic acid but not L-mimosine. (2-Methyl-4-[E,2Z)-3-phenyl-2-propenyliden]-1,3-oxazol-5(4H)-one (7) bearing a cinnamyol residue at C-4 of oxazolone moiety and an IC50 = 1.23 +/- 0.37 mu M was found to be the most active one among all tested compounds. These studies reveal that the substitution of functional group (s) at C-4 and C-2 positions plays a vital role in the activity of this series of compounds. It is concluded that compound 7 may act as a potential lead molecule to develop new drugs for the treatment of tyrosinase based disorders. (c) 2006 Elsevier Ltd. All rights reserved.