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The structures and absolute configurations of these compounds were elucidated by comprehensive spectroscopic analysis, including NMR, HRESIMS, SOR, TDDFT-ECD, and DP4+ probability analysis. The stereogenic centers at C-15 in related xeniaphyllanes were proposed for the first time based on comparative SOR analysis. Compounds 1 and 2 possess a tricyclic 4\/9-fused carbocyclic framework featuring an epoxide moiety, whereas compounds 3 and 4 exhibit related bicyclic scaffolds. A plausible biogenetic pathway originating from geranylgeranyl pyrophosphate (GGPP) was proposed to account for their structural diversity. Compounds 1 and 2 showed potent AChE inhibitory activity (IC50 = 1.7 and 4.4 \u03bcM, respectively), while being inactive against BChE and noncytotoxic toward normal cell lines (HEK293 and Vero). Mechanistic studies combining enzyme kinetics and molecular docking revealed that 1 and 2 act as mixed-type AChE inhibitors, with Ki values of 1.02 and 1.87 \u03bcM, respectively. These findings represent the first report of xeniaphyllane-type diterpenoids with potential for neurotherapeutic development.<\/jats:p>","DOI":"10.1021\/acs.jnatprod.6c00535","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:33:58Z","timestamp":1783607638000},"page":"2143-2156","source":"Crossref","is-referenced-by-count":2,"title":["Xeniaphyllane-Type Diterpenoids from the Soft Coral\n                    <i>Sclerophytum humesi<\/i>\n                    : Resolving Absolute Configurations\nand Anti-Alzheimer\u2019s Potential"],"prefix":"10.1021","volume":"89","author":[{"given":"Phuong Vu","family":"Luu","sequence":"first","affiliation":[{"name":"Taipei Medical University , , ,","place":["Taipei, Taiwan, 110301"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuong-Quoc","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Can Tho University , , ,","place":["Can Tho, Vietnam, 94000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huong Lien","family":"Ton-Nu","sequence":"additional","affiliation":[{"name":"Can Tho University , , ,","place":["Can Tho, Vietnam, 94000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thuy-Tien Thi","family":"Phan","sequence":"additional","affiliation":[{"name":"Taipei Medical University , , ,","place":["Taipei, Taiwan, 110301"]},{"name":"Binh Duong University , , Thu Dau Mot , ,","place":["Binh Duong, Vietnam, 820000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quoc-Dung Tran","family":"Huynh","sequence":"additional","affiliation":[{"name":"Binh Duong University , , Thu Dau Mot , ,","place":["Binh Duong, Vietnam, 820000"]},{"name":"Academia Sinica , , ,","place":["Taipei, Taiwan, 115024"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngoc-Thac","family":"Pham","sequence":"additional","affiliation":[{"name":"University of Medicine and Pharmacy at Ho Chi Minh City , , ,","place":["Ho Chi Minh City, Vietnam, 700000"]},{"name":"Taipei Medical University , , ,","place":["Taipei, Taiwan, 110301"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huong-Giang","family":"Le","sequence":"additional","affiliation":[{"name":"University of Medicine and Pharmacy at Ho Chi Minh City , , ,","place":["Ho Chi Minh City, Vietnam, 700000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lo-Yun","family":"Chen","sequence":"additional","affiliation":[{"name":"Taipei Medical University , , ,","place":["Taipei, Taiwan, 110301"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7849-8254","authenticated-orcid":true,"given":"Yu-Chia","family":"Chang","sequence":"additional","affiliation":[{"name":"Chang Gung University of Science and Technology , , ,","place":["Taoyuan, Taiwan, 333324"]},{"name":"Chang Gung University of Science and Technology , , ,","place":["Taoyuan City, Taiwan, 33303"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jui-Hsin","family":"Su","sequence":"additional","affiliation":[{"name":"National Museum of Marine Biology & Aquarium , ,","place":["Pingtung, Taiwan, 94450"]},{"name":"National Sun Yat-sen University , , ,","place":["Kaohsiung, Taiwan, 804"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Rong","family":"Peng","sequence":"additional","affiliation":[{"name":"Taipei Medical University , , ,","place":["Taipei, Taiwan, 110301"]},{"name":"Taipei Medical University , , ,","place":["Taipei, Taiwan, 110301"]},{"name":"Chang Gung University of Science and Technology , , ,","place":["Taoyuan, Taiwan, 333324"]},{"name":"Taipei Medical University , , ,","place":["Taipei, Taiwan, 110301"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7220-6356","authenticated-orcid":true,"given":"Kuei-Hung","family":"Lai","sequence":"additional","affiliation":[{"name":"Taipei Medical University , , ,","place":["Taipei, Taiwan, 110301"]},{"name":"Taipei Medical University , , ,","place":["Taipei, Taiwan, 110301"]},{"name":"National Museum of Marine Biology & Aquarium , ,","place":["Pingtung, Taiwan, 94450"]},{"name":"Taipei Medical University Hospital , , ,","place":["Taipei, Taiwan, 110301"]},{"name":"Taipei Medical University , , ,","place":["Taipei, Taiwan, 110301"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"issue":"77","key":"2026081111091848000_cit1","doi-asserted-by":"publisher","first-page":"77sr71","DOI":"10.1126\/scitranslmed.3002369","article-title":"Alzheimer\u2019s Disease: The Challenge\nof the Second Century","volume":"3","author":"Holtzman","year":"2011","journal-title":"Sci. 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