{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T01:52:17Z","timestamp":1783734737522,"version":"3.55.0"},"reference-count":31,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 108-2320-B-291-001-MY3"],"award-info":[{"award-number":["MOST 108-2320-B-291-001-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 110-2320-B-038-013"],"award-info":[{"award-number":["MOST 110-2320-B-038-013"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 110-2320-B-038-034"],"award-info":[{"award-number":["MOST 110-2320-B-038-034"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Education","award":["DP2-110-21121-01-N-12-03"],"award-info":[{"award-number":["DP2-110-21121-01-N-12-03"]}]},{"DOI":"10.13039\/501100004700","name":"Taipei Medical University","doi-asserted-by":"publisher","award":["TMU109-AE1-B15"],"award-info":[{"award-number":["TMU109-AE1-B15"]}],"id":[{"id":"10.13039\/501100004700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Marine sponges have been recognized as a rich source of potential anti-proliferative metabolites. Currently, there are two sponge-derived anti-cancer agents (a macrolide and a nucleoside) isolated from the Porifera phylum, suggesting the great potential of this sponge as a rich source for anti-neoplastic agents. To search for more bioactive metabolites from this phylum, we examined the EtOAc extract of Theonella sp. sponge. We isolated seven compounds (1\u20137), including four 4-methylene sterols (1\u20134), two nucleosides (5 and 6), and one macrolide (7). Among them, theonellasterol L (1) was identified for the first time, while 5\u2032-O-acetyl-2\u2032-deoxyuridine (5) and 5\u2032-O-acetylthymidine (6) were the first identified deoxyuridine and thymidine derivatives from the sponge Theonella sp. These structures were elucidated based on their spectroscopic data. The anti-proliferation activity of compounds 1\u20137 against the MCF-7, MDA-MB-231, T-47D, HCT-116, DLD-1, K562, and Molt 4 cancer cell lines was determined. The results indicated that the 14-\/15-oxygenated moiety played an important role in the antiproliferative activity and the macrolide derivatives dominated the anti-proliferative effect of the sponge Theonella sp. The in silico analysis, using a chemical global positioning system for natural products (ChemGPS-NP), indicated an anti-proliferative mode of actions (MOA) suggesting the potential applications of the isolated active metabolites as anti-proliferative agents.<\/jats:p>","DOI":"10.3390\/metabo11080532","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T22:40:31Z","timestamp":1628635231000},"page":"532","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Anti-Proliferative Potential of Secondary Metabolites from the Marine Sponge Theonella sp.: Moving from Correlation toward Causation"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7220-6356","authenticated-orcid":false,"given":"Kuei-Hung","family":"Lai","sequence":"first","affiliation":[{"name":"PhD Program in Clinical Drug Development of Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4537-1353","authenticated-orcid":false,"given":"Bo-Rong","family":"Peng","sequence":"additional","affiliation":[{"name":"National Museum of Marine Biology & Aquarium, Pingtung 94450, Taiwan"},{"name":"Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9144-8577","authenticated-orcid":false,"given":"Chun-Han","family":"Su","sequence":"additional","affiliation":[{"name":"Agricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El-Shazly","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, German University in Cairo, Cairo 11432, Egypt"},{"name":"Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, Ain-Shams University, Organization of African Unity Street, Abassia, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Long","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biological Science & Technology, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Cheng","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Biological Science & Technology, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ting","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nutrition, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Tzu","family":"Yen","sequence":"additional","affiliation":[{"name":"Department of Chinese Medicine, Sin-Lau Hospital, Tainan 70142, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lung-Shuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chinese Medicine, Sin-Lau Hospital, Tainan 70142, Taiwan"},{"name":"The School of Chinese Medicine for Post Baccalaureate, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jui-Hsin","family":"Su","sequence":"additional","affiliation":[{"name":"National Museum of Marine Biology & Aquarium, Pingtung 94450, Taiwan"},{"name":"Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dahiya, R., Dahiya, S., Kumar, P., Kumar, R.V., Dahiya, S., Kumar, S., Saharan, R., Basu, P., Mitra, A., and Sharma, A. 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