{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:37:30Z","timestamp":1787315850438,"version":"build-2736575974"},"reference-count":35,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Research and Development Projects of Hainan Province","award":["ZDYF2025SHFZ055"],"award-info":[{"award-number":["ZDYF2025SHFZ055"]}]},{"name":"Key Research and Development Projects of Hainan Province","award":["CARS-21"],"award-info":[{"award-number":["CARS-21"]}]},{"name":"Key Research and Development Projects of Hainan Province","award":["ZDKJ2021031"],"award-info":[{"award-number":["ZDKJ2021031"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["ZDYF2025SHFZ055"],"award-info":[{"award-number":["ZDYF2025SHFZ055"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["CARS-21"],"award-info":[{"award-number":["CARS-21"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["ZDKJ2021031"],"award-info":[{"award-number":["ZDKJ2021031"]}]},{"name":"Major Technology Project of Hainan Province","award":["ZDYF2025SHFZ055"],"award-info":[{"award-number":["ZDYF2025SHFZ055"]}]},{"name":"Major Technology Project of Hainan Province","award":["CARS-21"],"award-info":[{"award-number":["CARS-21"]}]},{"name":"Major Technology Project of Hainan Province","award":["ZDKJ2021031"],"award-info":[{"award-number":["ZDKJ2021031"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Aquisinenins G\u2013I (1\u20133), three new 2-(2-phenylethyl)chromone-sesquiterpene hybrids, were isolated from the ethanol extract of Hainan agarwood derived from Aquilaria sinensis. Spectroscopic techniques, such as 1D and 2D NMR and HRESIMS, were used to determine their structures. Experimental and computed ECD data were compared to confirm their absolute configurations. Compounds 1\u20133 are uncommon dimeric derivatives of 2-(2-phenylethyl)chromone-sesquiterpene, characterized by the fusion of 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone with agarofuran or agarospirane-type sesquiterpene units by an ester linkage. Compound 1 inhibited nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells, showing an IC50 value of 22.31 \u00b1 0.42 \u03bcM. The neuroprotective effects of compounds 1 and 3 against H2O2-induced apoptosis were assessed in human neuroblastoma SH-SY5Y cells. Compound 1 demonstrated cytotoxicity with IC50 values of 72.37 \u00b1 0.20 \u03bcM against K562 and 61.47 \u00b1 0.22 \u03bcM against BEL-7402, while compounds 2 and 3 showed cytotoxicity across all five tested human cancer cell lines.<\/jats:p>","DOI":"10.3390\/molecules30091984","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T05:05:57Z","timestamp":1745989557000},"page":"1984","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["2-(2-Phenylethyl)chromone-Sesquiterpene Hybrids from Agarwood of Aquilaria sinensis: Characterization and Biological Activity Evaluation"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3072-8798","authenticated-orcid":false,"given":"Guan-Hua","family":"Xu","sequence":"first","affiliation":[{"name":"Key Laboratory of Genetics and Germplasm Innovation of Tropical Special Forest Trees and Ornamental Plants, Ministry of Education, College of Tropical Agriculture and Forestry, Hainan University, Danzhou 571737, China"},{"name":"Key Laboratory of Natural Products Research and Development of Li Folk Medicine of Hainan Province, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Natural Products Research and Development of Li Folk Medicine of Hainan Province, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6838-6550","authenticated-orcid":false,"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Natural Products Research and Development of Li Folk Medicine of Hainan Province, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Qin","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Natural Products Research and Development of Li Folk Medicine of Hainan Province, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Hua","family":"Dong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Natural Products Research and Development of Li Folk Medicine of Hainan Province, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Zhuo","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Natural Products Research and Development of Li Folk Medicine of Hainan Province, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cai-Hong","family":"Cai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Natural Products Research and Development of Li Folk Medicine of Hainan Province, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Zhe","family":"Yuan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Natural Products Research and Development of Li Folk Medicine of Hainan Province, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Li","family":"Mei","sequence":"additional","affiliation":[{"name":"Key Laboratory of Natural Products Research and Development of Li Folk Medicine of Hainan Province, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shou-Bai","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Genetics and Germplasm Innovation of Tropical Special Forest Trees and Ornamental Plants, Ministry of Education, College of Tropical Agriculture and Forestry, Hainan University, Danzhou 571737, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Fu","family":"Dai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Natural Products Research and Development of Li Folk Medicine of Hainan Province, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.jep.2016.06.055","article-title":"Aquilaria spp. (agarwood) as source of health beneficial compounds: A review of traditional use, phytochemistry and pharmacology","volume":"189","author":"Hashim","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1039\/D0NP00042F","article-title":"Natural products in agarwood and Aquilaria plants: Chemistry, biological activities and biosynthesis","volume":"38","author":"Li","year":"2021","journal-title":"Nat. Prod. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5389","DOI":"10.1002\/ejoc.201200725","article-title":"Nine 2-(2-phenylethyl) chromone derivatives from the resinous wood of Aquilaria sinensis and their inhibition of LPS-induced NO production in RAW 264.7 cells","volume":"2012","author":"Chen","year":"2012","journal-title":"Eur. J. Org. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Chen, L.L., Liu, Y., Li, Y., Yin, W., and Cheng, Y. (2022). Anti-Cancer Effect of Sesquiterpene and Triterpenoids from Agarwood of Aquilaria sinensis. Molecules, 27.","DOI":"10.3390\/molecules27165350"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7643","DOI":"10.1021\/acs.joc.2c00145","article-title":"Sesquiterpenoid-Chromone Heterohybrids from Agarwood of Aquilaria sinensis as Potent Specific Smad3 Phosphorylation Inhibitors","volume":"87","author":"Huang","year":"2022","journal-title":"J. Org. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"8352","DOI":"10.1021\/acs.joc.3c00372","article-title":"Aquilariperoxide A, a Sesquiterpene Dimer from Agarwood of Aquilaria sinensis with Dual Antitumor and Antimalarial Effects","volume":"88","author":"Huang","year":"2023","journal-title":"J. Org. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s13659-021-00313-0","article-title":"Sesquiterpenoids and 2-(2-Phenylethyl)chromone Derivatives from the Resinous Heartwood of Aquilaria sinensis","volume":"11","author":"Wei","year":"2021","journal-title":"Nat. Prod. Bioprospect"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zhang, H., Ma, J.L., Chang, C., Ta, H., Zhao, Y.F., Shi, S.P., Song, Y.L., Tu, P.F., Huo, H.X., and Zheng, J. (2023). Gastroprotective 2-(2-phenylethyl)chromone-sesquiterpene hybrids from the resinous wood of Aquilaria sinensis (Lour.) Gilg. Bioorg. Chem., 133.","DOI":"10.1016\/j.bioorg.2023.106396"},{"key":"ref_9","first-page":"191","article-title":"Studies on the constituents of Aquilaria sinensis (Lour.) Gilg. I. Isolation and structure elucidation of two new sesquiterpenes, baimuxinic acid and baimuxinal","volume":"18","author":"Yang","year":"1983","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_10","first-page":"516","article-title":"Studies on the chemical constituents of Aquilaria sinensis (Lour.) Gilg. II. Isolation and structure of baimuxinol and dehydrobaimuxinol","volume":"21","author":"Yang","year":"1986","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_11","first-page":"635","article-title":"Study on the Chemical Constituents of Essential Oil of Aquilaria sinensis Lour Gilg","volume":"30","author":"Xu","year":"1988","journal-title":"J. Integr. Plant Biol."},{"key":"ref_12","first-page":"264","article-title":"Studies on the chemical constituents of Aquilaria sinensis (Lour) Gilg. III. Elucidation of the structure of isobaimuxinol and isolation and identification of the constituents of lower boiling fraction of the volatile oil","volume":"24","author":"Yang","year":"1989","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_13","first-page":"1973","article-title":"Sesquiterpenes and monoterpene from Aquilaria sinensis","volume":"37","author":"Yang","year":"2012","journal-title":"China J. Chin. Mater. Med."},{"key":"ref_14","first-page":"678","article-title":"Studies on the chemical constituents of Aquilaria sinensis (Lour.) Gilg. IV. Isolation and characterization of 2-(2-phenylethyl) chromone derivatives","volume":"24","author":"Yang","year":"1989","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_15","first-page":"186","article-title":"Studies on the chemical constituents of Aquilaria sinensis (Lour.) Gilg. V. Isolation and characterization of three 2-(2-phenylethyl) chromone derivatives","volume":"25","author":"Yang","year":"1990","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_16","first-page":"325","article-title":"Chemical constituents of Aquilaria sinensis (I)","volume":"37","author":"Liu","year":"2006","journal-title":"Chin. Tradit. Herb. Drugs"},{"key":"ref_17","first-page":"1138","article-title":"Chemical constituents of Lignum Aquilariae Resinatum (I)","volume":"38","author":"Liu","year":"2007","journal-title":"Chin. Tradit. Herb. Drugs"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.phytochem.2011.11.017","article-title":"2-(2-phenylethyl)chromones from Chinese eaglewood","volume":"76","author":"Yang","year":"2012","journal-title":"Phytochemistry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1080\/10286020903508424","article-title":"Two new 2-(2-phenylethyl)chromones from Chinese eaglewood","volume":"12","author":"Dai","year":"2010","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_20","first-page":"573","article-title":"Study on the chemical constituents from Chinese eaglewood in Hainan","volume":"18","author":"Mei","year":"2010","journal-title":"J. Trop. Subtrop."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1002\/hlca.201100442","article-title":"Two New 2-(2-Phenylethyl) chromen-4-ones from Aquilaria sinensis (Lour.) Gilg","volume":"95","author":"Gao","year":"2012","journal-title":"Helv. Chim. Acta"},{"key":"ref_22","first-page":"2070","article-title":"Spiroaquilarenes A\u2013E: Unprecedented anti-inflammatory sesquiterpene polymers from agarwood of Aquilaria sinensis","volume":"9","author":"Huang","year":"2022","journal-title":"J. Org. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"105422","DOI":"10.1016\/j.fitote.2022.105422","article-title":"Dimeric 2-(2-phenethyl)chromones from agarwood of Aquilaria filaria","volume":"165","author":"Yang","year":"2023","journal-title":"Fitoterapia"},{"key":"ref_24","first-page":"597","article-title":"Studies on the crystal structure of baimuxiangic acid","volume":"17","author":"He","year":"1982","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1021\/np500509q","article-title":"Anti-inflammatory ursane- and oleanane-type triterpenoids from Vitex negundo var","volume":"77","author":"Li","year":"2014","journal-title":"cannabifolia. J. Nat. Prod."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.phytol.2021.09.008","article-title":"Filarones A and B, new anti-inflammatory dimeric 2-(2-phenethyl) chromones from agarwood of Aquilaria filaria","volume":"46","author":"Liu","year":"2021","journal-title":"Phytochem. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.fitote.2019.01.008","article-title":"Seven new neuroprotective sesquineolignans isolated from the seeds of Crataegus pinnatifida","volume":"133","author":"Cheng","year":"2019","journal-title":"Fitoterapia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.fitote.2017.03.008","article-title":"Four new bi-2-(2-phenylethyl)chromone derivatives of agarwood from Aquilaria crassna","volume":"119","author":"Yang","year":"2017","journal-title":"Fitoterapia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.1002\/jcc.24922","article-title":"Automated and efficient quantum chemical determination and energetic ranking of molecular protonation sites","volume":"38","author":"Pracht","year":"2017","journal-title":"J. Comput. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1021\/acs.jctc.9b00143","article-title":"Exploration of Chemical Compound, Conformer, and Reaction Space with Meta-Dynamics Simulations Based on Tight-Binding Quantum Chemical Calculations","volume":"15","author":"Grimme","year":"2019","journal-title":"J. Chem. Theory Comput."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7169","DOI":"10.1039\/C9CP06869D","article-title":"Automated exploration of the low-energy chemical space with fast quantum chemical methods","volume":"22","author":"Pracht","year":"2020","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6551","DOI":"10.1039\/D1SC00621E","article-title":"Calculation of absolute molecular entropies and heat capacities made simple","volume":"12","author":"Pracht","year":"2021","journal-title":"Chem. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3174","DOI":"10.1021\/acs.jctc.2c00239","article-title":"Automated Molecular Cluster Growing for Explicit Solvation by Efficient Force Field and Tight Binding Methods","volume":"18","author":"Spicher","year":"2022","journal-title":"J. Chem. Theory Comput."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/jcc.22885","article-title":"Multiwfn: A multifunctional wavefunction analyzer","volume":"33","author":"Lu","year":"2012","journal-title":"J. Comput. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/9\/1984\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:24:24Z","timestamp":1760030664000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/9\/1984"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,29]]},"references-count":35,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["molecules30091984"],"URL":"https:\/\/doi.org\/10.3390\/molecules30091984","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,29]]}}}