Synthesis, cytotoxicity assay, and molecular docking study of hydroxychalcone derivatives as potential tyrosinase inhibitors

doi:10.5246/jcps.2021.08.051

Abstract

Abstract:

In this work, we studied the synthesis, cytotoxicity assay, and molecular docking of hydroxychalcone derivatives as tyrosinase inhibitors. Synthesis of chalcone derivatives was carried out through a Claisen-Schmidt condensation reaction between acetophenone and benzaldehyde derivatives under alkaline conditions for 48 h. The synthesized products were characterized by using Fourier transform infrared (FTIR), gas chromatography-mass spectrometry (GC-MS), proton and carbon nuclear magnetic resonance (¹H and ¹³C NMR) spectrometer. The in vitro inhibitory activity was evaluated against tyrosinase enzyme by employing L-3,4-dihydroxyphenylalanine (L-DOPA) as the substrate. We successfully synthesized 4-hydroxychalcone (HC) and 4-hydroxy-3-methoxychalcone (HMC) with a yield of 60% and 76%, respectively. While the tyrosinase inhibitory test of HC and HMC gave the IC₅₀ value of 64.35 and 21.56 μg/mL, respectively, demonstrating that their inhibitory activities against tyrosinase enzyme were better compared with kojic acid and hydroquinone as the positive controls. We also found that HC gave 2025 μg/mL as the IC₅₀ value against Vero cells, confirming that it was not toxic to the normal cell line. The molecular docking study gave the root-mean-square deviation value of less than 2 ?. Furthermore, the binding energies of hydroxychalcone derivatives were found as –30.13 and –31.38 kJ/mol, showing that those compounds could be potentially used as the alternative tyrosinase inhibitors in medical application.

Key words: Hydroxychalcone, Cytotoxicity, In vitro, Molecular docking, Tyrosinase inhibitors

Supporting:

Figure S1. Inhibition of tyrosinase enzyme by 4-hydroxychalcone, 4-hydroxy-3-methoxychalcone and hydroquinone compounds.

Aris Stiawan, Eti Nurwening Sholikhah, Yehezkiel Steven Kurniawan, Yoga Priastomo, Jumina. Synthesis, cytotoxicity assay, and molecular docking study of hydroxychalcone derivatives as potential tyrosinase inhibitors[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(8): 634-644.

Figures/Tables 11

Table 1. Tyrosinase enzyme inhibition activity by HC.

Table 2. Tyrosinase enzyme inhibition activity by HMC.

Table 3. Tyrosinase enzyme inhibition activity by hydroquinone.

Table 4. The IC50 value of HC, HMC and hydroquinone against tyrosinase enzyme.

Table 5. The IC50 value of HC and HMC against Vero cell lines.

Table 6. The bonding distance between compounds and important amino acid residues of 3NQ1 protein.

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