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. 2020 Apr 7;14(1):28.
doi: 10.1186/s13065-020-00679-1. eCollection 2020 Dec.

Synthesis, biological evaluation and molecular docking analysis of vaniline-benzylidenehydrazine hybrids as potent tyrosinase inhibitors

Aida Iraji  1 , Tina Adelpour  2 , Najmeh Edraki  1 , Mahsima Khoshneviszadeh  1 , Ramin Miri  1 , Mehdi Khoshneviszadeh  1   2
Affiliations

Synthesis, biological evaluation and molecular docking analysis of vaniline-benzylidenehydrazine hybrids as potent tyrosinase inhibitors

Aida Iraji et al. BMC Chem. .

Abstract

In this work, 11 novel compounds based on vaniline and benzylidenehydrazine structure were synthesized with various substituents on phenyl aromatic ring of the molecule and evaluated as tyrosinase inhibitors. These new derivatives showed significant anti-tyrosinase activities, among which 4i demonstrated to be the most potent compound, with IC50 values of 1.58 µM . The structure-activity relationship study of the novel constructed analogs was fully discussed. Kinetic study of compound 4i showed uncompetitive inhibition towards tyrosinase. Furthermore, the high potency of 4i was supported theoretically by molecular docking evaluations.

Keywords: Anti-tyrosinase agents; Kinetic study; Methoxybenzohydrazide; Molecular docking; Structure-based design.

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Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Design of new compounds targeting tyrosinase based on the hybridization strategies
Scheme 1
Scheme 1
Synthesis of (E)-Nʹ-benzylidene-4-hydroxy-3-methoxybenzohydrazide derivatives 4a–k
Fig. 2
Fig. 2
Para-substituted derivatives of benzylidene-4-hydroxy-3-methoxybenzohydrazide
Fig. 3
Fig. 3
Lineweaver–Burk plot for the inhibition of tyrosinase-catalyzed l-DOPA oxidation by 4i at 0, 10 and 25 µM
Fig. 4
Fig. 4
The binding mode of compound of 4i within mushroom tyrosinase (PDB ID: 2Y9X) active site. 4i is presented in orange. Only important residues for binding are shown. Hydrogen bonds interactions were depicted in green, van der Waals interaction were depicted in green, interaction with metal ions were depicted in the green line, π–π and π–aryl stacking interactions were depicted in pink
See this image and copyright information in PMC

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