Pub Date : 2025-12-22DOI: 10.1016/j.phytochem.2025.114758
Mochamad Muslich Arief , Nalae Kang , A-Young Shin , Soo-Jin Heo , Yeon-Ju Lee , Hyi-Seung Lee , Jihoon Lee
A chemical investigation of the Vietnamese marine sponge Aaptos sp. identified eight previously undescribed aaptamines (1–8) and two known analogs (9–10). In particular, derivatives (1–6) feature unusual oxygen-generated stereocenters at C-5 and C-6, rendering them the first examples of optically active aaptamines. The planar structures of 1–8 were elucidated based on interpretation of the 1D and 2D NMR spectra, combined with HRESIMS data. The relative and absolute configurations of 1–6 were determined by 1D NOE and electronic circular dichroism experiments, respectively. In addition, a series of oxidation studies on aaptamine (9) revealed that C-9 and Δ5 can be selectively oxidized under different reagent conditions, providing a potential indication of the biosynthetic pathway of compounds 1–6. Evaluation of the anticancer activities of isolates revealed that compounds 7 and 10 exhibited cytotoxicity against the AGS cell line with EC50 values of 8.95 μM and 5.98 μM, respectively.
{"title":"Isolation, structure elucidation, and absolute configuration of 5,6-dioxygenated aaptamine derivatives from the marine sponge Aaptos sp.","authors":"Mochamad Muslich Arief , Nalae Kang , A-Young Shin , Soo-Jin Heo , Yeon-Ju Lee , Hyi-Seung Lee , Jihoon Lee","doi":"10.1016/j.phytochem.2025.114758","DOIUrl":"10.1016/j.phytochem.2025.114758","url":null,"abstract":"<div><div>A chemical investigation of the Vietnamese marine sponge <em>Aaptos</em> sp. identified eight previously undescribed aaptamines (<strong>1</strong>–<strong>8</strong>) and two known analogs (<strong>9</strong>–<strong>10</strong>). In particular, derivatives (<strong>1</strong>–<strong>6</strong>) feature unusual oxygen-generated stereocenters at C-5 and C-6, rendering them the first examples of optically active aaptamines. The planar structures of <strong>1</strong>–<strong>8</strong> were elucidated based on interpretation of the 1D and 2D NMR spectra, combined with HRESIMS data. The relative and absolute configurations of <strong>1</strong>–<strong>6</strong> were determined by 1D NOE and electronic circular dichroism experiments, respectively. In addition, a series of oxidation studies on aaptamine (<strong>9</strong>) revealed that C-9 and Δ<sup>5</sup> can be selectively oxidized under different reagent conditions, providing a potential indication of the biosynthetic pathway of compounds <strong>1</strong>–<strong>6</strong>. Evaluation of the anticancer activities of isolates revealed that compounds <strong>7</strong> and <strong>10</strong> exhibited cytotoxicity against the AGS cell line with EC<sub>50</sub> values of 8.95 μM and 5.98 μM, respectively.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"244 ","pages":"Article 114758"},"PeriodicalIF":3.4,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-22DOI: 10.1016/j.phytochem.2025.114757
Qian Wu, Ren-Fen Ma, Hua Zhang
Fourteen previously unreported ent-abietane diterpenoids, named curviflorinoids A–N, comprising six intact, six mononor, and two trinor derivatives, were isolated from the twigs and leaves of Phlogacanthus curviflorus. Their structures with absolute configurations were established by spectroscopic means, comprising HR-ESIMS, NMR, ECD and single crystal X-ray crystallography. All of them except curviflorinoid N were evaluated for their inhibitory activity against the diabetic target α-glucosidase. Curviflorinoid D exhibited the most potent inhibition, with an IC50 value of 2.70 μM. The binding mode of curviflorinoid D to α-glucosidase was further investigated, which identified it as a mixed-type inhibitor.
{"title":"Ent-abietane diterpenoids with α-glucosidase inhibitory activity from Phlogacanthus curviflorus","authors":"Qian Wu, Ren-Fen Ma, Hua Zhang","doi":"10.1016/j.phytochem.2025.114757","DOIUrl":"10.1016/j.phytochem.2025.114757","url":null,"abstract":"<div><div>Fourteen previously unreported <em>ent</em>-abietane diterpenoids, named curviflorinoids A–N, comprising six intact, six mononor, and two trinor derivatives, were isolated from the twigs and leaves of <em>Phlogacanthus curviflorus</em>. Their structures with absolute configurations were established by spectroscopic means, comprising HR-ESIMS, NMR, ECD and single crystal X-ray crystallography. All of them except curviflorinoid N were evaluated for their inhibitory activity against the diabetic target <em>α</em>-glucosidase. Curviflorinoid D exhibited the most potent inhibition, with an IC<sub>50</sub> value of 2.70 μM. The binding mode of curviflorinoid D to <em>α</em>-glucosidase was further investigated, which identified it as a mixed-type inhibitor.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"244 ","pages":"Article 114757"},"PeriodicalIF":3.4,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-19DOI: 10.1016/j.phytochem.2025.114755
Quoc-Vu Pham , Yu-Chia Chang , You-Song Cheng , Yun-Shiuan Chen , Lo-Yun Chen , Mei-Hsien Lee , Jui-Hsin Su , Bo-Rong Peng , Kuei-Hung Lai , Tsong-Long Hwang
Marine sponges of the genus Lendenfeldia are known as a rich source of scalarane-type sesterterpenoids with diverse biological activities. In the present study, SMART-guided isolation of scalarane-type sesterterpenoids from the marine sponge Lendenfeldia sp. yielded a total of twelve members of this chemical class (1–12), including five previously undescribed compounds, named as lendenborvicins A–E (1–5). The structures of previously undescribed compounds were elucidated through comprehensive spectroscopic analyses, including 1D/2D NMR, HRESIMS, and ECD spectroscopy for the determination of absolute configurations. All isolated compounds were evaluated for their anti-osteoclastogenic activity using a TRAP assay in PMA/RANKL-induced THP-1 cells. Compounds 1, 2, 8, 10, 11, and 12 significantly reduced TRAP activity, with compound 11 exhibiting the strongest effect, decreasing TRAP activity to 64.75 ± 1.37 %. Based on these results, a structure–activity relationship (SAR) was preliminarily analyzed to identify the structural features contributing to the observed biological activity. This study provides the first documented evidence of anti-osteoclastogenic activity among scalarane-type sesterterpenoids.
海海绵是具有多种生物活性的角鲨烷型酯萜类化合物的丰富来源。在本研究中，通过智能引导从海绵Lendenfeldia sp.中分离出scalarane型酯萜类化合物（1-12），共获得12个该化学类的成员（1-12），其中包括5个先前未描述的化合物，命名为lendenborvicins a - e（1-5）。通过全面的光谱分析，包括1D/2D NMR， HRESIMS和ECD光谱来确定绝对构型，阐明了先前描述的化合物的结构。在PMA/ rankl诱导的THP-1细胞中，使用TRAP方法评估所有分离化合物的抗破骨活性。化合物1、2、8、10、11和12显著降低了TRAP活性，其中化合物11的作用最强，使TRAP活性降低了64.75±1.37%。基于这些结果，初步分析了构效关系（SAR），以确定与所观察到的生物活性有关的结构特征。这项研究提供了第一个文献证据，证明角鲨烷型酯萜类化合物具有抗破骨活性。
{"title":"SMART-assisted discovery of scalaranes from the marine sponge Lendenfeldia sp. and its anti-osteoclastogenesis activity","authors":"Quoc-Vu Pham , Yu-Chia Chang , You-Song Cheng , Yun-Shiuan Chen , Lo-Yun Chen , Mei-Hsien Lee , Jui-Hsin Su , Bo-Rong Peng , Kuei-Hung Lai , Tsong-Long Hwang","doi":"10.1016/j.phytochem.2025.114755","DOIUrl":"10.1016/j.phytochem.2025.114755","url":null,"abstract":"<div><div>Marine sponges of the genus <em>Lendenfeldia</em> are known as a rich source of scalarane-type sesterterpenoids with diverse biological activities. In the present study, SMART-guided isolation of scalarane-type sesterterpenoids from the marine sponge <em>Lendenfeldia</em> sp. yielded a total of twelve members of this chemical class (<strong>1</strong>–<strong>12</strong>), including five previously undescribed compounds, named as lendenborvicins A–E (<strong>1</strong>–<strong>5</strong>). The structures of previously undescribed compounds were elucidated through comprehensive spectroscopic analyses, including 1D/2D NMR, HRESIMS, and ECD spectroscopy for the determination of absolute configurations. All isolated compounds were evaluated for their anti-osteoclastogenic activity using a TRAP assay in PMA/RANKL-induced THP-1 cells. Compounds <strong>1</strong>, <strong>2</strong>, <strong>8</strong>, <strong>10</strong>, <strong>11</strong>, and <strong>12</strong> significantly reduced TRAP activity, with compound <strong>11</strong> exhibiting the strongest effect, decreasing TRAP activity to 64.75 ± 1.37 %. Based on these results, a structure–activity relationship (SAR) was preliminarily analyzed to identify the structural features contributing to the observed biological activity. This study provides the first documented evidence of anti-osteoclastogenic activity among scalarane-type sesterterpenoids.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"244 ","pages":"Article 114755"},"PeriodicalIF":3.4,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/j.phytochem.2025.114756
Phuong Vu Luu , Thuy-Tien Thi Phan , Ngoc-Thac Pham , Huong-Giang Le , Lo-Yun Chen , Huong Lien Ton-Nu , Mei-Hsien Lee , Yao-An Shen , Yu-Jui Fan , Yu-Chia Chang , Jui-Hsin Su , Bo-Rong Peng , Kuei-Hung Lai
Eight previously undescribed terpenoids, including six xeniaphyllane-derived diterpenoids, sclerohumins G-L (1–6), and two norcaryophyllene-type sesquiterpene isomers, norsclerohumins M and N (7 and 8), were isolated from the soft coral Sclerophytum humesi by MIMN-guided isolation. These compounds feature a 4/9-fused ring system, which was first isolated from the genus Sclerophytum. Moreover, compound 6 possesses a 20-exomethylene moiety, which is uncommon among xeniaphyllane-type diterpenoids. Their structures were elucidated through their spectroscopic analysis, including NMR, HR-ESI-MS, ECD, and DP4+ probability assessments. All isolates were tested for their cytotoxic activities, revealing that compounds 1–5 exhibited selective cytotoxicity in the MIA PaCa-2 cell line with IC50 values ranging from 9.0 to 26.1 μM and selective index (SI) greater than 3. The structure-activity relationships (SARs) of these active compounds were further investigated, providing insights into the molecular features that modulate cytotoxic efficacy. Additionally, a plausible biosynthetic pathway of compounds 1–6 was proposed, demonstrating the soft coral Sclerophytum humesi as a rich source of novel natural products.
{"title":"Sclerohumins G-L: Selective cytotoxic diterpenoids featuring a 4/9-fused ring system from the soft coral Sclerophytum humesi","authors":"Phuong Vu Luu , Thuy-Tien Thi Phan , Ngoc-Thac Pham , Huong-Giang Le , Lo-Yun Chen , Huong Lien Ton-Nu , Mei-Hsien Lee , Yao-An Shen , Yu-Jui Fan , Yu-Chia Chang , Jui-Hsin Su , Bo-Rong Peng , Kuei-Hung Lai","doi":"10.1016/j.phytochem.2025.114756","DOIUrl":"10.1016/j.phytochem.2025.114756","url":null,"abstract":"<div><div>Eight previously undescribed terpenoids, including six xeniaphyllane-derived diterpenoids, sclerohumins G-L (<strong>1–6</strong>), and two norcaryophyllene-type sesquiterpene isomers, norsclerohumins M and N (<strong>7</strong> and <strong>8</strong>), were isolated from the soft coral <em>Sclerophytum humesi</em> by MIMN-guided isolation. These compounds feature a 4/9-fused ring system, which was first isolated from the genus <em>Sclerophytum</em>. Moreover, compound <strong>6</strong> possesses a 20-exomethylene moiety, which is uncommon among xeniaphyllane-type diterpenoids. Their structures were elucidated through their spectroscopic analysis, including NMR, HR-ESI-MS, ECD, and DP4+ probability assessments. All isolates were tested for their cytotoxic activities, revealing that compounds <strong>1–5</strong> exhibited selective cytotoxicity in the MIA PaCa-2 cell line with IC<sub>50</sub> values ranging from 9.0 to 26.1 μM and selective index (SI) greater than 3. The structure-activity relationships (SARs) of these active compounds were further investigated, providing insights into the molecular features that modulate cytotoxic efficacy. Additionally, a plausible biosynthetic pathway of compounds <strong>1</strong>–<strong>6</strong> was proposed, demonstrating the soft coral <em>Sclerophytum humesi</em> as a rich source of novel natural products.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"244 ","pages":"Article 114756"},"PeriodicalIF":3.4,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-16DOI: 10.1016/j.phytochem.2025.114750
Shuang-Qin Cao , Ru-Yi Pan , Tong-Tong Zhang , Jian-Hong Gong , Meng Li , Hui Chen , Jing-Ke Zhang , Zhi-You Hao , Xiao-Ke Zheng , Yan-Jun Sun , Wei-Sheng Feng
Nine undescribed polyhydroxylated oleanane triterpenoids (cissatriterpenoids D-L, 1–9) were isolated from the roots of Cissampelos pareira var. hirsuta. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis (HR-ESI-MS, UV, IR, NMR), and compared with the spectral data reported in the literature. All the compounds were tested for their cytotoxicity against MGC-803 and B16F10 cell lines, and inhibitory activity against nitric oxide (NO) release in LPS-induced RAW 264.7 cells. Among the tested compounds, compound 3 demonstrated the most potent cytotoxicity against the B16F10 cell line, with an IC50 value of 28.58 μM (etoposide, 23.51 μM). Moreover, it also exhibited the strongest inhibition of NO production in LPS-stimulated RAW 264.7 cells with an IC50 value of 17.73 μM, and was equivalent to that of the control drug dexamethasone (17.95 μM, P > 0.05). Compared with etoposide (47.77 μM), compounds 3 and 4 showed more potent cytotoxicities against the MGC-803 cell line with IC50 values of 42.21 μM and 38.28 μM, respectively. The preliminary study of structure-activity relationship indicated that esterification of 28-OH by tiglic acid may enhance the cytotoxic activity against two cell lines and NO inhibition effect in LPS-stimulated RAW 264.7 cells of polyhydroxylated oleanane triterpenoids. In contrast, benzoylation of 28-OH was found to increase the cytotoxic activity of those compounds against MGC-803 cell line. These results revealed the potential of polyhydroxylated oleanane triterpenoids as lead compounds for anti-tumor and anti-inflammatory applications.
{"title":"Cissatriterpenoids D-L, nine undescribed polyhydroxylated oleanane triterpenoids from Cissampelos pareira var. hirsuta","authors":"Shuang-Qin Cao , Ru-Yi Pan , Tong-Tong Zhang , Jian-Hong Gong , Meng Li , Hui Chen , Jing-Ke Zhang , Zhi-You Hao , Xiao-Ke Zheng , Yan-Jun Sun , Wei-Sheng Feng","doi":"10.1016/j.phytochem.2025.114750","DOIUrl":"10.1016/j.phytochem.2025.114750","url":null,"abstract":"<div><div>Nine undescribed polyhydroxylated oleanane triterpenoids (cissatriterpenoids D-L, <strong>1</strong>–<strong>9</strong>) were isolated from the roots of <em>Cissampelos pareira</em> var. <em>h</em><em>irsuta</em>. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis (HR-ESI-MS, UV, IR, NMR), and compared with the spectral data reported in the literature. All the compounds were tested for their cytotoxicity against MGC-803 and B16F10 cell lines, and inhibitory activity against nitric oxide (NO) release in LPS-induced RAW 264.7 cells. Among the tested compounds, compound <strong>3</strong> demonstrated the most potent cytotoxicity against the B16F10 cell line, with an IC<sub>50</sub> value of 28.58 μM (etoposide, 23.51 μM). Moreover, it also exhibited the strongest inhibition of NO production in LPS-stimulated RAW 264.7 cells with an IC<sub>50</sub> value of 17.73 μM, and was equivalent to that of the control drug dexamethasone (17.95 μM, <em>P</em> > 0.05). Compared with etoposide (47.77 μM), compounds <strong>3</strong> and <strong>4</strong> showed more potent cytotoxicities against the MGC-803 cell line with IC<sub>50</sub> values of 42.21 μM and 38.28 μM, respectively. The preliminary study of structure-activity relationship indicated that esterification of 28-OH by tiglic acid may enhance the cytotoxic activity against two cell lines and NO inhibition effect in LPS-stimulated RAW 264.7 cells of polyhydroxylated oleanane triterpenoids. In contrast, benzoylation of 28-OH was found to increase the cytotoxic activity of those compounds against MGC-803 cell line. These results revealed the potential of polyhydroxylated oleanane triterpenoids as lead compounds for anti-tumor and anti-inflammatory applications.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"244 ","pages":"Article 114750"},"PeriodicalIF":3.4,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-16DOI: 10.1016/j.phytochem.2025.114754
Haiyan Chen , Yongjing Xu , Congcong Zhao , Xuli Tang , Xiao Han , Guoqiang Li
A rearranged diterpenoid with a previously undescribed 16/17(15 → 13)-diabeo carbon skeleton, sinusiaesenoid A (1), and a nitrogenous norxeniaphyllane-type diterpenoid possessing an unprecedented formylpyrrole moiety side chain, sinusiaesenoid B (2), together with eight previously undescribed xeniaphyllane-type and norxeniaphyllane-type diterpenoid sinusiaesenoids C-J (3–10), were isolated from the soft coral Sinularia siaesensis. Their structures were established by the spectroscopic analysis, X-ray diffraction analysis, DP4+ probability analysis, and calculated ECD. Compound 8 showed pro-angiogenic activity in zebrafish.
{"title":"Sinusiaesenoids A-J, previously undescribed diterpenoids with pro-angiogenic activity from the soft coral Sinularia siaesensis","authors":"Haiyan Chen , Yongjing Xu , Congcong Zhao , Xuli Tang , Xiao Han , Guoqiang Li","doi":"10.1016/j.phytochem.2025.114754","DOIUrl":"10.1016/j.phytochem.2025.114754","url":null,"abstract":"<div><div>A rearranged diterpenoid with a previously undescribed 16/17(15 → 13)-<em>diabeo</em> carbon skeleton, sinusiaesenoid A (<strong>1</strong>), and a nitrogenous norxeniaphyllane-type diterpenoid possessing an unprecedented formylpyrrole moiety side chain, sinusiaesenoid B (<strong>2</strong>), together with eight previously undescribed xeniaphyllane-type and norxeniaphyllane-type diterpenoid sinusiaesenoids C-J (<strong>3</strong>–<strong>10</strong>), were isolated from the soft coral <em>Sinularia siaesensis</em>. Their structures were established by the spectroscopic analysis, X-ray diffraction analysis, DP4+ probability analysis, and calculated ECD. Compound <strong>8</strong> showed pro-angiogenic activity in zebrafish.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"244 ","pages":"Article 114754"},"PeriodicalIF":3.4,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15DOI: 10.1016/j.phytochem.2025.114752
Chae-Yeong An , Chan-Woong Park , Pisey Pel , Piseth Khiev , Young-Won Chin
Bioassay-guided isolation using a HepG2 cell-based proprotein convertase subtilisin/kexin type 9 (PCSK9) ELISA led to the isolation of four previously unreported (1–4) and six known (5–10) mono-tetrahydrofuran Annonaceous acetogenins from the branches of Polyalthia evecta. The structures of all isolates were elucidated based on spectroscopic data analyses or chemical reaction including 1D and 2D NMR, HRESIMS, LC-MS/MS of the lithium adducts, ECD measurements and the modified Mosher's method. All isolates were evaluated for their PCSK9 secretion inhibitory activities, and a plausible structure–activity relationship was proposed. Among them, compound 5 (annonacin) significantly suppressed PCSK9 secretion as well as expressions of PCSK9 mRNA and protein. Moreover, this compound 5 enhanced LDL uptake, and mitigated atorvastatin-induced upregulation of PCSK9. This study represents the first investigation for the PCSK9 inhibitory potential of acetogenin-class compounds.
{"title":"Discovery of undescribed PCSK9 inhibitory activities in Annonaceous acetogenins from Polyalthia evecta","authors":"Chae-Yeong An , Chan-Woong Park , Pisey Pel , Piseth Khiev , Young-Won Chin","doi":"10.1016/j.phytochem.2025.114752","DOIUrl":"10.1016/j.phytochem.2025.114752","url":null,"abstract":"<div><div>Bioassay-guided isolation using a HepG2 cell-based proprotein convertase subtilisin/kexin type 9 (PCSK9) ELISA led to the isolation of four previously unreported (<strong>1</strong>–<strong>4</strong>) and six known (<strong>5</strong>–<strong>10</strong>) mono-tetrahydrofuran Annonaceous acetogenins from the branches of <em>Polyalthia evecta</em>. The structures of all isolates were elucidated based on spectroscopic data analyses or chemical reaction including 1D and 2D NMR, HRESIMS, LC-MS/MS of the lithium adducts, ECD measurements and the modified Mosher's method. All isolates were evaluated for their PCSK9 secretion inhibitory activities, and a plausible structure–activity relationship was proposed. Among them, compound <strong>5</strong> (annonacin) significantly suppressed PCSK9 secretion as well as expressions of PCSK9 mRNA and protein. Moreover, this compound <strong>5</strong> enhanced LDL uptake, and mitigated atorvastatin-induced upregulation of PCSK9. This study represents the first investigation for the PCSK9 inhibitory potential of acetogenin-class compounds.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"244 ","pages":"Article 114752"},"PeriodicalIF":3.4,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-14DOI: 10.1016/j.phytochem.2025.114751
Phuong-Thien Thuong , Thi-Kim-Quy Ha , Duy-Thuan Nguyen , Van-Tuan Vu , Jorge-Eduardo Ponce-Zea , Thi-Phuong Doan , Van-Hieu Mai , Won-Keun Oh
A comprehensive phytochemical investigation of the Vietnamese medicinal plant Gomphogyne bonii led to the isolation of ten saponins, including eight previously undescribed dammarane-type saponins (1–8) and the two known oleane-type saponins (9 and 10), using various chromatographic techniques. The chemical structures of all isolated compounds were elucidated based on extensive physicochemical properties and detailed spectroscopic analyses, including NMR and mass spectrometry. To evaluate their pharmacological potential, all compounds were subjected to biological assessment for insulin-mimetic activity using in vitro glucose uptake and AMP-activated protein kinase (AMPK) assays. The results revealed that compounds 1, and 7–10 significantly enhanced glucose uptake in differentiated 3T3-L1 adipocytes. Notably, compounds 1, 7, 9, and 10 also upregulated the expression of glucose transporter 4 (GLUT4) via AMPK activation. These findings represent the first report on the structural elucidation and biological activity of constituents from the Gomphogyne genus, highlighting their potential as novel agents for regulating glucose metabolism and as promising functional food ingredients for the management diabetes.
{"title":"1-Hydroxy dammarane triterpenoids from the aerial parts of Gomphogyne bonii enhance glucose uptake in 3T3-L1 adipocytes through activation of AMP-activated protein kinase","authors":"Phuong-Thien Thuong , Thi-Kim-Quy Ha , Duy-Thuan Nguyen , Van-Tuan Vu , Jorge-Eduardo Ponce-Zea , Thi-Phuong Doan , Van-Hieu Mai , Won-Keun Oh","doi":"10.1016/j.phytochem.2025.114751","DOIUrl":"10.1016/j.phytochem.2025.114751","url":null,"abstract":"<div><div>A comprehensive phytochemical investigation of the Vietnamese medicinal plant <em>Gomphogyne bonii</em> led to the isolation of ten saponins, including eight previously undescribed dammarane-type saponins (<strong>1</strong>–<strong>8</strong>) and the two known oleane-type saponins (<strong>9</strong> and <strong>10</strong>), using various chromatographic techniques. The chemical structures of all isolated compounds were elucidated based on extensive physicochemical properties and detailed spectroscopic analyses, including NMR and mass spectrometry. To evaluate their pharmacological potential, all compounds were subjected to biological assessment for insulin-mimetic activity using in vitro glucose uptake and AMP-activated protein kinase (AMPK) assays. The results revealed that compounds <strong>1</strong>, and <strong>7</strong>–<strong>10</strong> significantly enhanced glucose uptake in differentiated 3T3-L1 adipocytes. Notably, compounds <strong>1</strong>, <strong>7</strong>, <strong>9</strong>, and <strong>10</strong> also upregulated the expression of glucose transporter 4 (GLUT4) via AMPK activation. These findings represent the first report on the structural elucidation and biological activity of constituents from the <em>Gomphogyne</em> genus, highlighting their potential as novel agents for regulating glucose metabolism and as promising functional food ingredients for the management diabetes.</div></div>","PeriodicalId":20170,"journal":{"name":"Phytochemistry","volume":"244 ","pages":"Article 114751"},"PeriodicalIF":3.4,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-13DOI: 10.1016/j.phytochem.2025.114746
Xiangliu Chen , Ini Wong , Mengjing Cong , Weihao Chen , Meng Jin , Hong Wang , Fangfang Chen , Qingwen Zhang , Kechun Liu , Yonghong Liu , Rongchun Wang , Junjian Wang , Junfeng Wang
To explore bioactive specialized metabolites from marine-derived fungi, four previously undescribed 2-pyridone alkaloids, oxalicpyridones A–D (1–4), two unreported tetramic acids, tolypocladenols G and H (5 and 6), together with five known 2-pyridone derivatives (7–11), were isolated from the marine-derived fungus Penicillium oxalicum SCSIO 41320. Their structures, including absolute configurations, were elucidated by extensive nuclear magnetic resonance (NMR) spectroscopic analysis, X-ray single-crystal diffraction, and calculations of electronic circular dichroism (ECD), 13C NMR, and optical rotation (OR). Additionally, oxalicpyridones A–C (1–3) inhibited the viability of several small-cell lung cancer (SCLC) cell lines in a dose-dependent manner. Among them, oxalicpyridone A (1) not only inhibited proliferation, induced apoptosis, and suppressed metastasis of SCLC cells in vitro, but also significantly inhibited the growth of SCLC cell–derived xenograft tumors in zebrafish in vivo. Collectively, these findings enrich the chemical diversity of marine-derived 2-pyridone alkaloids and provide potential lead compounds for anticancer drug discovery.
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