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

Abstract

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 IC value 0.0371 ± 0.0018 μM as compared to the reference kojic acid (IC = 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.

Biological and Cheminformatics Studies of Newly Designed Triazole Based Derivatives as Potent Inhibitors against Mushroom Tyrosinase

“…The predicted chemo-informatic properties such as molecular weight (g/mol) HBD, HBA, LogP, polar surface area (PSA), molar volume and a drug-likeness score of ligand molecules were obtained. It has been confirmed from previous research data that the standard value for molecular weight is (≤500 g/mol) [ 19 ]. The computational results showed that our compounds possessed good molecular weight compared to the standard value (500 g/mol).…”

A comprehensive review on tyrosinase inhibitors

“…So far, several azole derivatives (Figure 13) have been studied for their tyrosinase inhibitory activity 388 . The discovered new types of inhibitors included DL-3(5-benzazolyl) alanines and alpha-methyldopa analogs 389 , aryl pyrazoles 390 , heterocyclic hybrids based on pyrazole and thiazolidinone scaffolds 391 , 3,5-diaryl-4,5-dihydro-1H 392 and 3,5-diaryl pyrazole derivatives 393 , pyrazolo[4,3-e][1,2,4]triazine sulfonamides and sildenafil 394–396 , 1,3-oxazine-tetrazole 397 , indole-spliced thiadiazole 398 , benzimidazole-1,2,3-triazole hybrids 399 , 1,2,3-triazole-linked coumarinopyrazole conjugates 400 , isoxazolone derivatives 401 5(4H)-oxazolone derivative 402 , imidazolium ionic liquids 403 , thiazolyl resorcinols 404 have demonstrated the inhibitory effect on tyrosinase. Furthermore, some thiazolidine derivatives have been evaluated for their tyrosinase inhibitory activity including azo-hydrazone tautomeric dyes substituted by thiazolidinone moiety 405 , (Z)-5-(2,4-dihydroxybenzylidene) thiazolidine-2,4-dione 406 , 5-(substituted benzylidene) thiazolidine-2,4-dione derivatives 407 , (2RS,4R)-2-(2,4-dihydroxyphenyl)thiazolidine-4-carboxylic acid 408 , 2-(substituted phenyl) thiazolidine-4-carboxylic acid derivatives 409 and (Z)-5-(3-hydroxy-4-methoxybenzylidene)-2-iminothiazolidin-4-one 410 .…”

Molecular Docking, Synthesis, and Tyrosinase Inhibition Activity of Acetophenone Amide: Potential Inhibitor of Melanogenesis

“…Over the past several years, our laboratory has reported various phenolic derivatives including tyramine, thymol, vanillin, carvacrol, and coumarin analogues which structurally mimic the natural substrates of the enzyme tyrosinase stronger than the L-tyrosine and L-DOPA [26][27][28][29][30]. We concluded from these investigations that substitution pattern of phenolic hydroxyls is directly related to degree of tyrosinase inhibition.…”