{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:23:19Z","timestamp":1791404599249,"version":"4.3.3"},"reference-count":49,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,2,10]],"date-time":"2019-02-10T00:00:00Z","timestamp":1549756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>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 D3 and D4 receptors. The half maximal effective concentration (EC50) of eckol for the dopamine D3 and D4 receptors was 48.62 \u00b1 3.21 and 42.55 \u00b1 2.54 \u00b5M, respectively, while the EC50 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, \u03c0\u2013alkyl, and \u03c0\u2013\u03c0 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 D3\/D4 agonist for the management of neurodegenerative diseases, such as Parkinson\u2019s disease.<\/jats:p>","DOI":"10.3390\/md17020108","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T03:18:20Z","timestamp":1549941500000},"page":"108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Eckol as a Potential Therapeutic against Neurodegenerative Diseases Targeting Dopamine D3\/D4 Receptors"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8482-1129","authenticated-orcid":false,"given":"Pradeep","family":"Paudel","sequence":"first","affiliation":[{"name":"Department of Food and Life Science, Pukyong National University, Busan 48513, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Hui","family":"Seong","sequence":"additional","affiliation":[{"name":"Department of Food and Life Science, Pukyong National University, Busan 48513, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangwook","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physics, Pukyong National University, Busan 48513, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Physics, Pukyong National University, Busan 48513, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Ah","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju 54896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9034-8868","authenticated-orcid":false,"given":"Jae Sue","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Food and Life Science, Pukyong National University, Busan 48513, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/nrd.2017.178","article-title":"Trends in GPCR drug discovery: New agents, targets and indications","volume":"16","author":"Hauser","year":"2017","journal-title":"Nat. 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