Journal of Chinese Pharmaceutical Sciences ›› 2021, Vol. 30 ›› Issue (8): 634-644.DOI: 10.5246/jcps.2021.08.051

• Original articles • Previous Articles     Next Articles

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

Aris Stiawan1, Eti Nurwening Sholikhah2, Yehezkiel Steven Kurniawan1,3, Yoga Priastomo1, Jumina1,*()   

  1. 1 Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
    2 Department of Pharmacology and Therapy, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
    3 Ma Chung Research Center for Photosynthetic Pigments, Universitas Ma Chung, Villa Puncak Tidar N-01, Malang 65151, Indonesia
  • Received:2020-12-06 Revised:2021-03-18 Accepted:2021-04-13 Online:2021-08-29 Published:2021-08-29
  • Contact: Jumina


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


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