Novel 1,3-oxazine-tetrazole hybrids as mushroom tyrosinase inhibitors and free radical scavengers: Synthesis, kinetic mechanism, and molecular docking studies

摘要

A variety of 5-(2H-tetrazol-5-yl)-4-thioxo-2-(substituted phenyl)-4,5-dihydro-1,3-oxazin-6-ones (3a-k) have been synthesized from 1,3-oxazine-5-carbonitriles (2a-k). The protocol represents an efficient, facile, and novel route from easily available precursors to unprecedented structures that share 1,3-oxazine and tetrazole motifs of utmost value. All the synthesized compounds (3a-k) were evaluated for their inhibitory potential against mushroom tyrosinase. Results revealed that all examined 1,3-oxazine-tetrazole hybrids exhibited significant tyrosinase inhibitory activity while compound 3d having 2-bromophenyl moiety was the most potent among the series with IC50 value 0.0371 +/- 0.0018 mu M as compared to the reference kojic acid (IC50 = 16.832 +/- 0.73 mu M). Inhibitory kinetics showed that compound 3d behaves as a competitive inhibitor. The molecular docking analysis was performed against target protein to investigate the binding mode. Moreover, compounds 3j and 3k displayed superior DPPH radical scavenging activity than other analogues.