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Novel 1,3‐oxazine‐tetrazole hybrids as mushroom tyrosinase inhibitors and free radical scavengers: Synthesis, kinetic mechanism, and molecular docking studies
Author(s) -
Qamar Rabia,
Saeed Aamer,
Larik Fayaz Ali,
Abbas Qamar,
Hassan Mubashir,
Raza Hussain,
Seo SungYum
Publication year - 2019
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13352
Subject(s) - tetrazole , chemistry , tyrosinase , moiety , stereochemistry , docking (animal) , kojic acid , dpph , ic50 , combinatorial chemistry , enzyme , biochemistry , antioxidant , in vitro , medicine , nursing
A variety of 5‐(2 H ‐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 IC 50 value 0.0371 ± 0.0018 μM as compared to the reference kojic acid ( IC 50 = 16.832 ± 0.73 μM). 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.