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(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.
Molecules. 2020 Nov 21; 25(22)M

Abstract

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 µM and 0.28 µM for the monophenolase and diphenolase as substrates in comparison to kojic acid as standard compound 19.97 µM and 33.47 µM. Moreover, the enzyme kinetics of compound 8 were determined to be of the mixed inhibition type and inhibition constant (Ki) values of 0.012 µM and 0.165 µM 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 α-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.

Authors+Show Affiliations

College of Pharmacy, Pusan National University, Busan 46241, Korea.College of Pharmacy, Pusan National University, Busan 46241, Korea.College of Pharmacy, Pusan National University, Busan 46241, Korea.College of Pharmacy, Pusan National University, Busan 46241, Korea.College of Pharmacy, Pusan National University, Busan 46241, Korea.College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, Gimhae, Gyeongnam 50834, Korea.College of Pharmacy, Pusan National University, Busan 46241, Korea.College of Pharmacy, Pusan National University, Busan 46241, Korea.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33233397

Citation

Jung, Hee Jin, et al. "(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." Molecules (Basel, Switzerland), vol. 25, no. 22, 2020.
Jung HJ, Noh SG, Ryu IY, et al. (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. Molecules. 2020;25(22).
Jung, H. J., Noh, S. G., Ryu, I. Y., Park, C., Lee, J. Y., Chun, P., Moon, H. R., & Chung, H. Y. (2020). (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. Molecules (Basel, Switzerland), 25(22). https://doi.org/10.3390/molecules25225460
Jung HJ, et al. (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. Molecules. 2020 Nov 21;25(22) PubMed PMID: 33233397.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - (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. AU - Jung,Hee Jin, AU - Noh,Sang Gyun, AU - Ryu,Il Young, AU - Park,Chaeun, AU - Lee,Ji Young, AU - Chun,Pusoon, AU - Moon,Hyung Ryong, AU - Chung,Hae Young, Y1 - 2020/11/21/ PY - 2020/10/22/received PY - 2020/11/12/revised PY - 2020/11/18/accepted PY - 2020/11/25/entrez PY - 2020/11/26/pubmed PY - 2020/11/26/medline KW - furan-chalcone KW - melanogenesis KW - molecular dynamics KW - tyrosinase inhibitor JF - Molecules (Basel, Switzerland) JO - Molecules VL - 25 IS - 22 N2 - 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 µM and 0.28 µM for the monophenolase and diphenolase as substrates in comparison to kojic acid as standard compound 19.97 µM and 33.47 µM. Moreover, the enzyme kinetics of compound 8 were determined to be of the mixed inhibition type and inhibition constant (Ki) values of 0.012 µM and 0.165 µM 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 α-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. SN - 1420-3049 UR - https://www.unboundmedicine.com/medline/citation/33233397/_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_ L2 - https://www.mdpi.com/resolver?pii=molecules25225460 DB - PRIME DP - Unbound Medicine ER -