Eckol as a Potential Therapeutic against Neurodegenerative Diseases Targeting Dopamine D<sub>3</sub>/D<sub>4</sub> Receptors
The G protein-coupled receptor (GPCR) family of proteins comprises signaling proteins that mediate cellular responses to various hormones and neurotransmitters, and serves as a prime target for drug discovery. Towards our goal of discovering secondary metabolites from natural sources that can functi...
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| Format: | Article |
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MDPI AG
2019-02-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/17/2/108 |
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| author | Pradeep Paudel Su Hui Seong Sangwook Wu Suhyun Park Hyun Ah Jung Jae Sue Choi |
| author_facet | Pradeep Paudel Su Hui Seong Sangwook Wu Suhyun Park Hyun Ah Jung Jae Sue Choi |
| author_sort | Pradeep Paudel |
| collection | DOAJ |
| description | The G protein-coupled receptor (GPCR) family of proteins comprises signaling proteins that mediate cellular responses to various hormones and neurotransmitters, and serves as a prime target for drug discovery. Towards our goal of discovering secondary metabolites from natural sources that can function as neuronal drugs, we evaluated the modulatory effect of eckol on various GPCRs via cell-based functional assays. In addition, we conducted in silico predictions to obtain molecular insights into the functional effects of eckol. Functional assays revealed that eckol had a concentration-dependent agonist effect on dopamine D<sub>3</sub> and D<sub>4</sub> receptors. The half maximal effective concentration (EC<sub>50</sub>) of eckol for the dopamine D<sub>3</sub> and D<sub>4</sub> receptors was 48.62 ± 3.21 and 42.55 ± 2.54 µM, respectively, while the EC<sub>50</sub> values of dopamine as a reference agonist for these two receptors were 2.9 and 3.3 nM, respectively. In silico studies revealed that a low binding energy in addition to hydrophilic, hydrophobic, π⁻alkyl, and π⁻π T-shaped interactions are potential mechanisms by which eckol binds to the dopamine receptors to exert its agonist effects. Molecular dynamics (MD) simulation revealed that Phe346 of the dopamine receptors is important for binding of eckol, similar to eticlopride and dopamine. Our results collectively suggest that eckol is a potential D<sub>3</sub>/D<sub>4</sub> agonist for the management of neurodegenerative diseases, such as Parkinson’s disease. |
| first_indexed | 2024-12-10T07:44:51Z |
| format | Article |
| id | doaj.art-90032b0ab28b44bbb481f83f6f1fb7c6 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-12-10T07:44:51Z |
| publishDate | 2019-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-90032b0ab28b44bbb481f83f6f1fb7c62022-12-22T01:57:12ZengMDPI AGMarine Drugs1660-33972019-02-0117210810.3390/md17020108md17020108Eckol as a Potential Therapeutic against Neurodegenerative Diseases Targeting Dopamine D<sub>3</sub>/D<sub>4</sub> ReceptorsPradeep Paudel0Su Hui Seong1Sangwook Wu2Suhyun Park3Hyun Ah Jung4Jae Sue Choi5Department of Food and Life Science, Pukyong National University, Busan 48513, KoreaDepartment of Food and Life Science, Pukyong National University, Busan 48513, KoreaDepartment of Physics, Pukyong National University, Busan 48513, KoreaDepartment of Physics, Pukyong National University, Busan 48513, KoreaDepartment of Food Science and Human Nutrition, Chonbuk National University, Jeonju 54896, KoreaDepartment of Food and Life Science, Pukyong National University, Busan 48513, KoreaThe G protein-coupled receptor (GPCR) family of proteins comprises signaling proteins that mediate cellular responses to various hormones and neurotransmitters, and serves as a prime target for drug discovery. Towards our goal of discovering secondary metabolites from natural sources that can function as neuronal drugs, we evaluated the modulatory effect of eckol on various GPCRs via cell-based functional assays. In addition, we conducted in silico predictions to obtain molecular insights into the functional effects of eckol. Functional assays revealed that eckol had a concentration-dependent agonist effect on dopamine D<sub>3</sub> and D<sub>4</sub> receptors. The half maximal effective concentration (EC<sub>50</sub>) of eckol for the dopamine D<sub>3</sub> and D<sub>4</sub> receptors was 48.62 ± 3.21 and 42.55 ± 2.54 µM, respectively, while the EC<sub>50</sub> values of dopamine as a reference agonist for these two receptors were 2.9 and 3.3 nM, respectively. In silico studies revealed that a low binding energy in addition to hydrophilic, hydrophobic, π⁻alkyl, and π⁻π T-shaped interactions are potential mechanisms by which eckol binds to the dopamine receptors to exert its agonist effects. Molecular dynamics (MD) simulation revealed that Phe346 of the dopamine receptors is important for binding of eckol, similar to eticlopride and dopamine. Our results collectively suggest that eckol is a potential D<sub>3</sub>/D<sub>4</sub> agonist for the management of neurodegenerative diseases, such as Parkinson’s disease.https://www.mdpi.com/1660-3397/17/2/108eckolGPCR-targetingdopamine agonistParkinson’s disease |
| spellingShingle | Pradeep Paudel Su Hui Seong Sangwook Wu Suhyun Park Hyun Ah Jung Jae Sue Choi Eckol as a Potential Therapeutic against Neurodegenerative Diseases Targeting Dopamine D<sub>3</sub>/D<sub>4</sub> Receptors Marine Drugs eckol GPCR-targeting dopamine agonist Parkinson’s disease |
| title | Eckol as a Potential Therapeutic against Neurodegenerative Diseases Targeting Dopamine D<sub>3</sub>/D<sub>4</sub> Receptors |
| title_full | Eckol as a Potential Therapeutic against Neurodegenerative Diseases Targeting Dopamine D<sub>3</sub>/D<sub>4</sub> Receptors |
| title_fullStr | Eckol as a Potential Therapeutic against Neurodegenerative Diseases Targeting Dopamine D<sub>3</sub>/D<sub>4</sub> Receptors |
| title_full_unstemmed | Eckol as a Potential Therapeutic against Neurodegenerative Diseases Targeting Dopamine D<sub>3</sub>/D<sub>4</sub> Receptors |
| title_short | Eckol as a Potential Therapeutic against Neurodegenerative Diseases Targeting Dopamine D<sub>3</sub>/D<sub>4</sub> Receptors |
| title_sort | eckol as a potential therapeutic against neurodegenerative diseases targeting dopamine d sub 3 sub d sub 4 sub receptors |
| topic | eckol GPCR-targeting dopamine agonist Parkinson’s disease |
| url | https://www.mdpi.com/1660-3397/17/2/108 |
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