Newly Designed Quinazolinone Derivatives as Novel Tyrosinase Inhibitor: Synthesis, Inhibitory Activity, and Mechanism
We synthesized a series of quinazolinone derivates as tyrosinase inhibitors and evaluated their inhibition constants. We synthesized 2-(2,6-dimethylhepta-1,5-dien-1-yl)quinazolin-4(3<i>H</i>)-one (Q1) from the natural citral. The concentration, which led to 50% activity loss of Q1, was 1...
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MDPI AG
2022-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/17/5558 |
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| author | Yaru Huang Jiefang Yang Yunyang Chi Chun Gong Haikuan Yang Fanxin Zeng Fang Gao Xiaoju Hua Zongde Wang |
| author_facet | Yaru Huang Jiefang Yang Yunyang Chi Chun Gong Haikuan Yang Fanxin Zeng Fang Gao Xiaoju Hua Zongde Wang |
| author_sort | Yaru Huang |
| collection | DOAJ |
| description | We synthesized a series of quinazolinone derivates as tyrosinase inhibitors and evaluated their inhibition constants. We synthesized 2-(2,6-dimethylhepta-1,5-dien-1-yl)quinazolin-4(3<i>H</i>)-one (Q1) from the natural citral. The concentration, which led to 50% activity loss of Q1, was 103 ± 2 μM (IC<sub>50</sub> = 103 ± 2 μM). Furthermore, we considered Q1 to be a mixed-type and reversible tyrosinase inhibitor, and determined the K<sub>I</sub> and K<sub>IS</sub> inhibition constants to be 117.07 μM and 423.63 μM, respectively. Our fluorescence experiment revealed that Q1 could interact with the substrates of tyrosine and L-DOPA in addition to tyrosinase. Molecular docking studies showed that the binding of Q1 to tyrosinase was driven by hydrogen bonding and hydrophobicity. Briefly, the current study confirmed a new tyrosinase inhibitor, which is expected to be developed into a novel pigmentation drug. |
| first_indexed | 2024-03-10T01:29:52Z |
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| id | doaj.art-9b28992366434c098e0b2651edbe7532 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T01:29:52Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-9b28992366434c098e0b2651edbe75322023-11-23T13:44:05ZengMDPI AGMolecules1420-30492022-08-012717555810.3390/molecules27175558Newly Designed Quinazolinone Derivatives as Novel Tyrosinase Inhibitor: Synthesis, Inhibitory Activity, and MechanismYaru Huang0Jiefang Yang1Yunyang Chi2Chun Gong3Haikuan Yang4Fanxin Zeng5Fang Gao6Xiaoju Hua7Zongde Wang8East China Woody Fragrance and Flavor Engineering Research Center of National Forestry and Grassland Administration, College of Forestry, Jiangxi Agricultural University, Nanchang 330045, ChinaJiangxi Academy of Forestry, Camphor Engineering Research Center of National Forestry and Grassland Administration, Nanchang 330032, ChinaJiangxi Academy of Forestry, Camphor Engineering Research Center of National Forestry and Grassland Administration, Nanchang 330032, ChinaJiangxi Academy of Forestry, Camphor Engineering Research Center of National Forestry and Grassland Administration, Nanchang 330032, ChinaJiangxi Academy of Forestry, Camphor Engineering Research Center of National Forestry and Grassland Administration, Nanchang 330032, ChinaJiangxi Academy of Forestry, Camphor Engineering Research Center of National Forestry and Grassland Administration, Nanchang 330032, ChinaYongfeng County Natural Resources Bureau, Ji’an 331500, ChinaJiangxi Academy of Forestry, Camphor Engineering Research Center of National Forestry and Grassland Administration, Nanchang 330032, ChinaEast China Woody Fragrance and Flavor Engineering Research Center of National Forestry and Grassland Administration, College of Forestry, Jiangxi Agricultural University, Nanchang 330045, ChinaWe synthesized a series of quinazolinone derivates as tyrosinase inhibitors and evaluated their inhibition constants. We synthesized 2-(2,6-dimethylhepta-1,5-dien-1-yl)quinazolin-4(3<i>H</i>)-one (Q1) from the natural citral. The concentration, which led to 50% activity loss of Q1, was 103 ± 2 μM (IC<sub>50</sub> = 103 ± 2 μM). Furthermore, we considered Q1 to be a mixed-type and reversible tyrosinase inhibitor, and determined the K<sub>I</sub> and K<sub>IS</sub> inhibition constants to be 117.07 μM and 423.63 μM, respectively. Our fluorescence experiment revealed that Q1 could interact with the substrates of tyrosine and L-DOPA in addition to tyrosinase. Molecular docking studies showed that the binding of Q1 to tyrosinase was driven by hydrogen bonding and hydrophobicity. Briefly, the current study confirmed a new tyrosinase inhibitor, which is expected to be developed into a novel pigmentation drug.https://www.mdpi.com/1420-3049/27/17/5558tyrosinaseinhibitorcitralderivativesfluorescence quenchingmolecular docking |
| spellingShingle | Yaru Huang Jiefang Yang Yunyang Chi Chun Gong Haikuan Yang Fanxin Zeng Fang Gao Xiaoju Hua Zongde Wang Newly Designed Quinazolinone Derivatives as Novel Tyrosinase Inhibitor: Synthesis, Inhibitory Activity, and Mechanism Molecules tyrosinase inhibitor citral derivatives fluorescence quenching molecular docking |
| title | Newly Designed Quinazolinone Derivatives as Novel Tyrosinase Inhibitor: Synthesis, Inhibitory Activity, and Mechanism |
| title_full | Newly Designed Quinazolinone Derivatives as Novel Tyrosinase Inhibitor: Synthesis, Inhibitory Activity, and Mechanism |
| title_fullStr | Newly Designed Quinazolinone Derivatives as Novel Tyrosinase Inhibitor: Synthesis, Inhibitory Activity, and Mechanism |
| title_full_unstemmed | Newly Designed Quinazolinone Derivatives as Novel Tyrosinase Inhibitor: Synthesis, Inhibitory Activity, and Mechanism |
| title_short | Newly Designed Quinazolinone Derivatives as Novel Tyrosinase Inhibitor: Synthesis, Inhibitory Activity, and Mechanism |
| title_sort | newly designed quinazolinone derivatives as novel tyrosinase inhibitor synthesis inhibitory activity and mechanism |
| topic | tyrosinase inhibitor citral derivatives fluorescence quenching molecular docking |
| url | https://www.mdpi.com/1420-3049/27/17/5558 |
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