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 μM, whereas standard inhibitors l-mimosine and kojic acid have IC50 values 3.68 ± 0.02 and 16.67 ± 0.52 μM,, 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 μM 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.

Seventeen oxazolone derivatives were synthesized, characterized, and screened for tyrosinase inhibition.Figure optionsDownload as PowerPoint slide