(E)-1-(Furan-2-yl)-(substituted phenyl)prop-2-en-1-one Derivatives as Tyrosinase Inhibitors and Melanogenesis Inhibition: An In Vitro and In Silico Study

被引:14
作者
Jung, Hee Jin [1 ]
Noh, Sang Gyun [1 ]
Ryu, Il Young [1 ]
Park, Chaeun [1 ]
Lee, Ji Young [1 ]
Chun, Pusoon [2 ,3 ]
Moon, Hyung Ryong [1 ]
Chung, Hae Young [1 ]
机构
[1] Pusan Natl Univ, Coll Pharm, Busan 46241, South Korea
[2] Inje Univ, Coll Pharm, Gimhae 50834, Gyeongnam, South Korea
[3] Inje Univ, Inje Inst Pharmaceut Sci & Res, Gimhae 50834, Gyeongnam, South Korea
基金
新加坡国家研究基金会;
关键词
furan-chalcone; melanogenesis; molecular dynamics; tyrosinase inhibitor; CHALCONES; POTENT; FURAN;
D O I
10.3390/molecules25225460
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A series of (E)-1-(furan-2-yl)prop-2-en-1-one derivatives (compounds 1-8) were synthesized and evaluated for their mushroom tyrosinase inhibitory activity. Among these series, compound 8 (2,4-dihydroxy group bearing benzylidene) showed potent tyrosinase inhibitory activity, with respective IC50 values of 0.0433 mu M and 0.28 mu M for the monophenolase and diphenolase as substrates in comparison to kojic acid as standard compound 19.97 mu M and 33.47 mu M. Moreover, the enzyme kinetics of compound 8 were determined to be of the mixed inhibition type and inhibition constant (K-i) values of 0.012 mu M and 0.165 mu M using the Lineweaver-Burk plot. Molecular docking results indicated that compound 8 can bind to the catalytic and allosteric sites 1 and 2 of tyrosinase to inhibit enzyme activity. The computational molecular dynamics analysis further revealed that compound 8 interacted with two residues in the tyrosinase active site pocket, such as ASN260 and MET280. In addition, compound 8 attenuated melanin synthesis and cellular tyrosinase activity, simulated by alpha-melanocyte-stimulating hormone and 1-methyl-3-isobutylxanthine. Compound 8 also decreased tyrosinase expressions in B16F10 cells. Based on in vitro and computational studies, we propose that compound 8 might be a worthy candidate for the development of an antipigmentation agent.
引用
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页数:17
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