engleski

In silico study of the tyrosinase inhibitory potential of arbutin and other bioactive compounds from strawberry tree (Arbutus unedo L.)

Tyrosinase is an enzyme involved in generation of dopamine-quinones, which has an important role in oxidative stress associated with different health disorders. It is also a common molecular target for the design of anti-melanogenic agents. Strawberry tree (Arbutus unedo L.) leaves are used in Mediterranean folk medicine to treat urinary tract infections, where arbutin is recognized as the main bioactive compound [1]. The inhibition of tyrosinase might be responsible for the intracellular antioxidant activity of arbutin. Moreover, other compounds from strawberry tree leaves, fruits and honey such as hyperoside and homogentisic acid [2] might inhibit tyrosinase owing to presence of phenolic group(s) as pharmacophore. Herein, we performed virtual screening of 25 compounds including β-arbutin (naturally occurring compound), α-arbutin (synthetic substance), 13 synthesizable arbutin derivatives designed using DrugSpaceX [3], other compounds from strawberry tree [4], and kojic acid as a positive control. 3D structures were optimized on PM7 level, and then were docked into the active site of Bacillus megaterium tyrosinase (pdb 3NQ1) using AutoDock Vina 1.1 [5]. The binding mode of β-arbutin is stabilized via hydrogen bond donor interactions with His231, His42, His60, Arg209, Gly216, and Asn205, hydrogen bond acceptor interaction with Arg209, and hydrophobic interactions with His208, Val218 and Ala221 (Figure 1). The binding energy (BE) of β- arbutin is -5.9 kcal/mol. Hyperoside and two arbutin derivatives (DA8 and DA14, Figure 1) interact more favorably with tyrosinase with the BE of -6.7, -7.2 and -7.3 kcal/mol, respectively. The results of this study provide a valuable structural insights into the molecular mechanisms of biological action of arbutin and other bioactives from strawberry tree, and might be exploited to develop more potent and drug-like analogues. References: 1. Jurica, K. et al, Journal of Herbal Medicine, 2017, 8, 17-23 ; 2. Jurič, A. et al, Chemico-Biological Interactions, 2021, 349, 109672 ; 3. Yang, T. et al, Nucleic Acids Research, 2021, 49(D1), D1170-D1178 ; 4. Brčić Karačonji, I. et al, Plants 2022, 11, 25 ; 5. Trott, O. et al, Journal of Computational Chemistry, 2010, 31, 455- 461. Acknowledgment: This research was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Contract number 451-03-68/2022-14/200168).

arbutin, tyrosinase, docking

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