1. Academic Validation
  2. Highly potent tyrosinase inhibitor, neorauflavane from Campylotropis hirtella and inhibitory mechanism with molecular docking

Highly potent tyrosinase inhibitor, neorauflavane from Campylotropis hirtella and inhibitory mechanism with molecular docking

  • Bioorg Med Chem. 2016 Jan 15;24(2):153-9. doi: 10.1016/j.bmc.2015.11.040.
Xuefei Tan 1 Yeong Hun Song 1 Chanin Park 2 Ki-Won Lee 2 Jeong Yoon Kim 1 Dae Wook Kim 1 Kwang Dong Kim 2 Keun Woo Lee 2 Marcus J Curtis-Long 3 Ki Hun Park 4
Affiliations

Affiliations

  • 1 Division of Applied Life Science (BK21 plus), IALS, Gyeongsang National University, Jinju 660-701, Republic of Korea.
  • 2 Division of Applied Life Science (BK21 plus), PMBBRC, RINS, Gyeongsang National University, Jinju 660-701, Republic of Korea.
  • 3 Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, United States.
  • 4 Division of Applied Life Science (BK21 plus), IALS, Gyeongsang National University, Jinju 660-701, Republic of Korea. Electronic address: khpark@gnu.ac.kr.
Abstract

Tyrosinase inhibition may be a means to alleviate not only skin hyperpigmentation but also neurodegeneration associated with Parkinson's disease. In the course of metabolite analysis from Tyrosinase inhibitory methanol extract (80% inhibition at 20 μg/ml) of Campylotropis hirtella, we isolated fourteen phenolic compounds, among which neorauflavane 3 emerged as a lead structure for Tyrosinase inhibition. Neorauflavane 3 inhibited Tyrosinase monophenolase activity with an IC50 of 30 nM. Thus this compound is 400-fold more active than kojic acid. It also inhibited diphenolase (IC50=500 nM), significantly. Another potent inhibitor 1 (IC50=2.9 μM) was found to be the most abundant metabolite in C. hirtella. In kinetic studies, compounds 3 showed competitive inhibitory behavior against both monophenolase and diphenolase. It manifested simple reversible slow-binding inhibition against monophenolase with the following kinetic parameters: Ki(app)=1.48 nM, k3=0.0033 nM(-1) min(-1) and k4=0.0049 min(-1). Neorauflavane 3 efficiently reduced melanin content in B16 melanoma cells with 12.95 μM of IC50. To develop a pharmacophore model, we explored the binding mode of neuroflavane 3 in the active site of Tyrosinase. Docking results show that resorcinol motif of B-ring and methoxy group in A-ring play crucial roles in the binding the Enzyme.

Keywords

Campylotropis hirtella; Competitive inhibitor; Molecular docking; Neorauflavane; Tyrosinase.

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