{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T02:42:25Z","timestamp":1779331345477,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T00:00:00Z","timestamp":1631750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010218","name":"Department of Science and Technology, Philippines","doi-asserted-by":"publisher","award":["DOST-SEI, DOST-PCHRD"],"award-info":[{"award-number":["DOST-SEI, DOST-PCHRD"]}],"id":[{"id":"10.13039\/501100010218","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>We report the first isolation of the alkaloid aaptamine from the Philippine marine sponge Stylissa sp. Aaptamine possessed weak antiproliferative activity against HCT116 colon cancer cells and inhibited the proteasome in vitro at 50 \u00b5M. These activities may be functionally linked. Due to its known, more potent activity on certain G-protein coupled receptors (GPCRs), including \u03b1-adrenergic and \u03b4-opioid receptors, the compound was profiled more broadly at sub-growth inhibitory concentrations against a panel of 168 GPCRs to potentially reveal additional targets and therapeutic opportunities. GPCRs represent the largest class of drug targets. The primary screen at 20 \u00b5M using the \u03b2-arrestin functional assay identified the antagonist, agonist, and potentiators of agonist activity of aaptamine. Dose-response analysis validated the \u03b1-adrenoreceptor antagonist activity of aaptamine (ADRA2C, IC50 11.9 \u00b5M) and revealed the even more potent antagonism of the \u03b2-adrenoreceptor (ADRB2, IC50 0.20 \u00b5M) and dopamine receptor D4 (DRD4, IC50 6.9 \u00b5M). Additionally, aaptamine showed agonist activity on selected chemokine receptors, by itself (CXCR7, EC50 6.2 \u00b5M; CCR1, EC50 11.8 \u00b5M) or as a potentiator of agonist activity (CXCR3, EC50 31.8 \u00b5M; CCR3, EC50 16.2 \u00b5M). These GPCRs play a critical role in the treatment of cardiovascular disease, diabetes, cancer, and neurological disorders. The results of this study may thus provide novel preventive and therapeutic strategies for noncommunicable diseases (NCDs).<\/jats:p>","DOI":"10.3390\/molecules26185618","type":"journal-article","created":{"date-parts":[[2021,9,18]],"date-time":"2021-09-18T00:13:47Z","timestamp":1631924027000},"page":"5618","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["GPCR Pharmacological Profiling of Aaptamine from the Philippine Sponge Stylissa sp. Extends Its Therapeutic Potential for Noncommunicable Diseases"],"prefix":"10.3390","volume":"26","author":[{"given":"Harmie","family":"Luyao","sequence":"first","affiliation":[{"name":"Department of Chemistry, Mindanao State University\u2014Iligan Institute of Technology, Iligan City 9200, Philippines"},{"name":"Department of Medicinal Chemistry and Center for Natural Products, Drug Discovery, and Development (CNPD3), University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4091-7492","authenticated-orcid":false,"given":"Hendrik","family":"Luesch","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Center for Natural Products, Drug Discovery, and Development (CNPD3), University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mylene","family":"Uy","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Mindanao State University\u2014Iligan Institute of Technology, Iligan City 9200, Philippines"},{"name":"Premier Research Institute of Science and Mathematics (PRISM), Mindanao State University\u2014Iligan Institute of Technology, Iligan City 9200, Philippines"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5555","DOI":"10.1016\/S0040-4039(00)85893-1","article-title":"Isolation and structure of aaptamine a novel heteroaromatic substance possessing \u03b1-blocking activity from the sea sponge Aaptos aaptos","volume":"23","author":"Nakamura","year":"1982","journal-title":"Tetrahedron Lett."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/0305-1978(91)90016-S","article-title":"Aaptamine, a taxonomic marker for sponges of the order hadromerida","volume":"19","author":"Bergquist","year":"1991","journal-title":"Biochem. 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