Oncogenic mutant p53 is one of the targets for cancer therapy, and the development of anticancer drugs that reactivate mutant p53 is a promising strategy. The extract of fungus Pestalotiopsis sp. changed mutant p53 to wild-type-like p53 in Saos-2 (p53R175H) cells, as shown by fluorescent immunostaining, and bioassay-guided purification of the extract afforded new dimeric epoxyquinoids, pestones A and B (1 and 2), and a known compound, rosnecatrone (3). The relative and absolute configurations of 1 and 2 were determined based on the spectroscopic data and semisynthesis from 3. Compounds 1 and 2 altered the conformation of mutant p53 in Saos-2 (p53R175H) cells, as shown by immunofluorescence staining. The cellular thermal shift assay analysis showed that 1 increased the thermostability of mutant p53 in Saos-2 (p53R175H) cells, suggesting the direct binding of 1 to mutant p53. Compounds 1 and 2 exhibited cytotoxic activities against Saos-2 (p53R175H) cells with IC50 values of 1.0 and 1.1 μM, respectively. Compound 1 was found to induce apoptosis in Saos-2 (p53R175H) cells by flow cytometry analysis and decreased tumor growth in vivo using a mouse model with HuCCT1 (p53R175H) cells.
{"title":"Pestones A and B from a Fungus <i>Pestalotiopsis</i> sp. Bound to Mutant p53 and Changed Its Conformation.","authors":"Yusaku Sadahiro, Misaki Okubo, Yuki Hitora, Natsuko Hitora-Imamura, Shunsuke Kotani, Sachiko Tsukamoto","doi":"10.1021/acs.jnatprod.4c01440","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01440","url":null,"abstract":"<p><p>Oncogenic mutant p53 is one of the targets for cancer therapy, and the development of anticancer drugs that reactivate mutant p53 is a promising strategy. The extract of fungus <i>Pestalotiopsis</i> sp. changed mutant p53 to wild-type-like p53 in Saos-2 (p53<sup>R175H</sup>) cells, as shown by fluorescent immunostaining, and bioassay-guided purification of the extract afforded new dimeric epoxyquinoids, pestones A and B (<b>1</b> and <b>2</b>), and a known compound, rosnecatrone (<b>3</b>). The relative and absolute configurations of <b>1</b> and <b>2</b> were determined based on the spectroscopic data and semisynthesis from <b>3</b>. Compounds <b>1</b> and <b>2</b> altered the conformation of mutant p53 in Saos-2 (p53<sup>R175H</sup>) cells, as shown by immunofluorescence staining. The cellular thermal shift assay analysis showed that <b>1</b> increased the thermostability of mutant p53 in Saos-2 (p53<sup>R175H</sup>) cells, suggesting the direct binding of <b>1</b> to mutant p53. Compounds <b>1</b> and <b>2</b> exhibited cytotoxic activities against Saos-2 (p53<sup>R175H</sup>) cells with IC<sub>50</sub> values of 1.0 and 1.1 μM, respectively. Compound <b>1</b> was found to induce apoptosis in Saos-2 (p53<sup>R175H</sup>) cells by flow cytometry analysis and decreased tumor growth <i>in vivo</i> using a mouse model with HuCCT1 (p53<sup>R175H</sup>) cells.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424622","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}
Ten previously undescribed iridoid glycosides (1-10), including monoiridoids, hybrid iridoid-alkaloids, bis-iridoids, noriridoid-iridoid dimers, and tetramers, were isolated from the roots of Gomphandra mollis Merr. Structural elucidation revealed unique sugar chains not previously observed for iridoids and complex tetrameric configurations that are rare in nature. Compounds 9, 10, and 15 demonstrated significant anti-inflammatory effects, with IC50 values ranging from 6.13 to 13.0 μM, and compounds 6, 7, and 11-13 showed notable hepatoprotective activity in HepG2 cells. Additionally, structure-activity relationship (SAR) analysis on anti-inflammatory effects was also conducted. This study enriches the structural database of iridoids, particularly complex derivatives, and highlights their therapeutic potential in addressing inflammation-related and liver diseases.
{"title":"Anti-inflammatory and Hepatoprotective Iridoid Glycosides from the Roots of <i>Gomphandra mollis</i>.","authors":"Quoc-Dung Tran Huynh, Thuy-Tien Thi Phan, Ta-Wei Liu, Thanh-Vu Nguyen, Truc-Ly Thi Duong, Su-Jung Hsu, Man-Hsiu Chu, Yun-Han Wang, Bien-Thuy Nguyen Bui, Dang-Khoa Nguyen, Thanh-Hoa Vo, Ching-Kuo Lee","doi":"10.1021/acs.jnatprod.4c01484","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01484","url":null,"abstract":"<p><p>Ten previously undescribed iridoid glycosides (<b>1</b>-<b>10</b>), including monoiridoids, hybrid iridoid-alkaloids, bis-iridoids, noriridoid-iridoid dimers, and tetramers, were isolated from the roots of <i>Gomphandra mollis</i> Merr. Structural elucidation revealed unique sugar chains not previously observed for iridoids and complex tetrameric configurations that are rare in nature. Compounds <b>9</b>, <b>10</b>, and <b>15</b> demonstrated significant anti-inflammatory effects, with IC<sub>50</sub> values ranging from 6.13 to 13.0 μM, and compounds <b>6</b>, <b>7</b>, and <b>11</b>-<b>13</b> showed notable hepatoprotective activity in HepG2 cells. Additionally, structure-activity relationship (SAR) analysis on anti-inflammatory effects was also conducted. This study enriches the structural database of iridoids, particularly complex derivatives, and highlights their therapeutic potential in addressing inflammation-related and liver diseases.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412370","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 : 2025-02-13DOI: 10.1021/acs.jnatprod.4c00834
Chenyang Lu, Samantha Nelson, Gabriela Coy, Chris Neumann, Elizabeth I Parkinson, Christopher A Rice
Balamuthia mandrillaris is a pathogenic free-living amoeba (pFLA) that can cause infection of the central nervous system (CNS), called Balamuthia amoebic encephalitis (BAE), as well as cutaneous and systemic diseases. Patients infected with B. mandrillaris have a high mortality rate due to a lack of effective treatments. A nonoptimized antimicrobial drug regimen is typically recommended; however, it has poor antiparasitic activity and can cause various and severe side effects. Cyclic peptides exhibit a broad spectrum of antimicrobial activities but are underexplored for their antiamoebic activity. In this study, we evaluated the anti-B. mandrillaris effect of Synthetic Natural Product Inspired Cyclic Peptides (SNaPP) mined from ∼500 biosynthetic gene clusters of various bacterial species. The predicted natural product-43 (pNP-43; BICyP1), identified from the SNaPP library, and its derivates displayed a significant inhibition against B. mandrillaris trophozoites, with five pNPs having IC50s ≤ 5 μM. Furthermore, all hit natural product inspired peptides demonstrated minimal to no hemolytic and cytotoxic effects on human red blood cells (RBCs) and immortalized human carcinoma cells, respectfully. Our study is the first to demonstrate the anti-B. mandrillaris effects of cyclic peptides, offering a promising new direction for drug development.
{"title":"Cyclic Peptide Natural Product Inspired Inhibitors of the Free-Living Amoeba <i>Balamuthia mandrillaris</i>.","authors":"Chenyang Lu, Samantha Nelson, Gabriela Coy, Chris Neumann, Elizabeth I Parkinson, Christopher A Rice","doi":"10.1021/acs.jnatprod.4c00834","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00834","url":null,"abstract":"<p><p><i>Balamuthia mandrillaris</i> is a pathogenic free-living amoeba (pFLA) that can cause infection of the central nervous system (CNS), called <i>Balamuthia</i> amoebic encephalitis (BAE), as well as cutaneous and systemic diseases. Patients infected with <i>B. mandrillaris</i> have a high mortality rate due to a lack of effective treatments. A nonoptimized antimicrobial drug regimen is typically recommended; however, it has poor antiparasitic activity and can cause various and severe side effects. Cyclic peptides exhibit a broad spectrum of antimicrobial activities but are underexplored for their antiamoebic activity. In this study, we evaluated the anti-<i>B. mandrillaris</i> effect of Synthetic Natural Product Inspired Cyclic Peptides (SNaPP) mined from ∼500 biosynthetic gene clusters of various bacterial species. The predicted natural product-43 (pNP-43; BICyP1), identified from the SNaPP library, and its derivates displayed a significant inhibition against <i>B. mandrillaris</i> trophozoites, with five pNPs having IC<sub>50</sub>s ≤ 5 μM. Furthermore, all hit natural product inspired peptides demonstrated minimal to no hemolytic and cytotoxic effects on human red blood cells (RBCs) and immortalized human carcinoma cells, respectfully. Our study is the first to demonstrate the anti-<i>B. mandrillaris</i> effects of cyclic peptides, offering a promising new direction for drug development.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412371","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 : 2025-02-12DOI: 10.1021/acs.jnatprod.5c00120
Shu-Xi Jing, Ran Fu, Chun-Huan Li, Cedric L Hugelshofer, Yi-Ming Shi, Shi-Hong Luo, Yan-Chun Liu, Yan Liu, Sheng-Hong Li
{"title":"Correction to \"Discovery of Unusual Sesterterpenoids from <i>Colquhounia coccinea</i> var. <i>mollis</i> and Their Metabolic Implications\".","authors":"Shu-Xi Jing, Ran Fu, Chun-Huan Li, Cedric L Hugelshofer, Yi-Ming Shi, Shi-Hong Luo, Yan-Chun Liu, Yan Liu, Sheng-Hong Li","doi":"10.1021/acs.jnatprod.5c00120","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00120","url":null,"abstract":"","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397554","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 : 2025-02-12DOI: 10.1021/acs.jnatprod.4c01172
Van-Hieu Mai, Seri Choi, Jorge-Eduardo Ponce-Zea, Thuong T T Nguyen, Hyung-Sik Kang, Heejung Yang, Hyang Burm Lee, Won-Keun Oh
Autophagy is a primary cellular mechanism that entails the degradation and recycling of impaired or redundant cellular constituents. It plays an essential role in maintaining cellular health and homeostasis. Dysfunction in autophagy has been implicated in a wide range of diseases, including cancer, cardiovascular diseases, and neurodegenerative diseases. A total of 200 fungal extracts were screened for their ability to modulate autophagy in HEK293A cells, a human kidney cell line stably expressing GFP-tagged LC3, a marker of autophagy. A potential autophagy regulator extract was identified from the freshwater-derived fungus, Talaromyces gwangjuensis. Through the implementation of Feature-Based Molecular Networking (FBMN), seven cyclodepsipeptides (1-7) and four lactone derivatives (8-11) were isolated from the bioactive fractions. The chemical structure of the newly isolated compounds, arthrichitins E-H (1-4) and gwangjupones A-D (8-11), were elucidated using 1D and 2D NMR spectroscopy, Marfey's analysis, J-based configuration analysis, ECD, and DP4+ probability calculations. Compounds 1, 4, and 6 were found to stimulate autophagic flux in IMR90 cells infected with an adeno-associated virus carrying an mCherry-GFP-LC3 construct, highlighting their potential as autophagy activators.
{"title":"Cyclodepsipeptides and Fatty Acid Lactones from the Freshwater-Derived Fungus, <i>Talaromyces gwangjuensis</i>, and Their Potential as Autophagy Activators.","authors":"Van-Hieu Mai, Seri Choi, Jorge-Eduardo Ponce-Zea, Thuong T T Nguyen, Hyung-Sik Kang, Heejung Yang, Hyang Burm Lee, Won-Keun Oh","doi":"10.1021/acs.jnatprod.4c01172","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01172","url":null,"abstract":"<p><p>Autophagy is a primary cellular mechanism that entails the degradation and recycling of impaired or redundant cellular constituents. It plays an essential role in maintaining cellular health and homeostasis. Dysfunction in autophagy has been implicated in a wide range of diseases, including cancer, cardiovascular diseases, and neurodegenerative diseases. A total of 200 fungal extracts were screened for their ability to modulate autophagy in HEK293A cells, a human kidney cell line stably expressing GFP-tagged LC3, a marker of autophagy. A potential autophagy regulator extract was identified from the freshwater-derived fungus, <i>Talaromyces gwangjuensis</i>. Through the implementation of Feature-Based Molecular Networking (FBMN), seven cyclodepsipeptides (<b>1</b>-<b>7</b>) and four lactone derivatives (<b>8</b>-<b>11</b>) were isolated from the bioactive fractions. The chemical structure of the newly isolated compounds, arthrichitins E-H (<b>1</b>-<b>4</b>) and gwangjupones A-D (<b>8</b>-<b>11</b>), were elucidated using 1D and 2D NMR spectroscopy, Marfey's analysis, <i>J</i>-based configuration analysis, ECD, and DP4+ probability calculations. Compounds <b>1</b>, <b>4</b>, and <b>6</b> were found to stimulate autophagic flux in IMR90 cells infected with an adeno-associated virus carrying an mCherry-GFP-LC3 construct, highlighting their potential as autophagy activators.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397601","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 : 2025-02-11DOI: 10.1021/acs.jnatprod.4c01377
Benson Oloya, Jane Namukobe, Mandy Krüger, Willy Ssengooba, Eric Sperlich, George Kwesiga, Kevin Komakech, Matthias Heydenreich, Robert Byamukama, Bernd Schmidt
trans-Fagaramide (1) and adubangoamide (2) are natural products with a cinnamic acid amide skeleton that have recently been isolated from Zanthoxylum leprieurii, a medicinal plant used locally in Uganda for the treatment of tuberculosis. Insufficient quantities of material from the natural source originally prevented the antimycobacterial evaluation of the new natural product 2. Herein, a synthesis of 2 is reported, and its antimycobacterial activity was determined using the synthetic material. Adubangoamide (2) is three times more active against the drug-susceptible M. tuberculosis strain H37Rv than trans-fagaramide (1), with an MIC value of 10.0 μM. In addition, we synthesized eight non-natural analogues of trans-fagaramide (1, MIC = 32.0 μM against H37Rv strain), in which benzylamide groups mimic the isobutylamide part of the trans-fagaramide structure. Five out of eight synthetic analogues are more active than the parent natural product: 11b (MIC = 6.0 μM), 11d (21.0 μM), 11e (6.1 μM), 11g (17.0 μM), and 11h (4.5 μM).
{"title":"Antimycobacterial Activities of the <i>Zanthoxylum leprieurii</i> Metabolite Adubangoamide and Non-Natural Fagaramide Analogues.","authors":"Benson Oloya, Jane Namukobe, Mandy Krüger, Willy Ssengooba, Eric Sperlich, George Kwesiga, Kevin Komakech, Matthias Heydenreich, Robert Byamukama, Bernd Schmidt","doi":"10.1021/acs.jnatprod.4c01377","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01377","url":null,"abstract":"<p><p><i>trans</i>-Fagaramide (<b>1</b>) and adubangoamide (<b>2</b>) are natural products with a cinnamic acid amide skeleton that have recently been isolated from <i>Zanthoxylum leprieurii</i>, a medicinal plant used locally in Uganda for the treatment of tuberculosis. Insufficient quantities of material from the natural source originally prevented the antimycobacterial evaluation of the new natural product <b>2</b>. Herein, a synthesis of <b>2</b> is reported, and its antimycobacterial activity was determined using the synthetic material. Adubangoamide (<b>2</b>) is three times more active against the drug-susceptible <i>M. tuberculosis</i> strain H<sub>37</sub>Rv than <i>trans</i>-fagaramide (<b>1</b>), with an MIC value of 10.0 μM. In addition, we synthesized eight non-natural analogues of <i>trans</i>-fagaramide (<b>1</b>, MIC = 32.0 μM against H<sub>37</sub>Rv strain), in which benzylamide groups mimic the isobutylamide part of the <i>trans</i>-fagaramide structure. Five out of eight synthetic analogues are more active than the parent natural product: <b>11b</b> (MIC = 6.0 μM), <b>11d</b> (21.0 μM), <b>11e</b> (6.1 μM), <b>11g</b> (17.0 μM), and <b>11h</b> (4.5 μM).</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389511","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 : 2025-02-11DOI: 10.1021/acs.jnatprod.4c01009
Seong Mi Lee, Hyung Won Ryu, Hyoung-Geun Kim, Yang Hee Jo, Kyoung Jin Park, Su Ui Lee, Eun Sol Oh, Sang Woo Lee, Sangho Choi, Wan-Yi Li, Bang Yeon Hwang, Sei-Ryang Oh
As part of an ongoing search for new anti-inflammatory agents from medicinal plants, five new dimeric and trimeric flavonoids (1-5) were isolated from the roots of Pistacia weinmannifolia. The structures of pistachalcone A (1), pistachalcone B (2), pistaflavanone A (3), pistachalcone C (4), and pistachalcone D (5) were elucidated by the analysis of spectroscopic data. The known compounds rhuschalcone II (6), rhuschalcone VI (7), and pauferrol B (8) were also isolated and identified. Our in vitro analysis found that compounds isolated from P. weinmannifolia root extract exert anti-inflammatory effects in phorbol myristate acetate (PMA)-induced NCI-H292 airway epithelial cells by the suppression of expression levels such as interleukin-8 (IL-8) and mucin 5AC (MUC5AC), which are closely related to the pulmonary inflammatory response in the pathogenesis of COPD. Therefore, these dihydrochalcone derivatives may have value as new starting materials for the development of drug candidates against COPD.
{"title":"Anti-Inflammatory Dimeric and Trimeric Flavonoids from the Roots of<i>Pistacia weinmannifolia</i>.","authors":"Seong Mi Lee, Hyung Won Ryu, Hyoung-Geun Kim, Yang Hee Jo, Kyoung Jin Park, Su Ui Lee, Eun Sol Oh, Sang Woo Lee, Sangho Choi, Wan-Yi Li, Bang Yeon Hwang, Sei-Ryang Oh","doi":"10.1021/acs.jnatprod.4c01009","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01009","url":null,"abstract":"<p><p>As part of an ongoing search for new anti-inflammatory agents from medicinal plants, five new dimeric and trimeric flavonoids (<b>1</b>-<b>5</b>) were isolated from the roots of <i>Pistacia weinmannifolia</i>. The structures of pistachalcone A (<b>1</b>), pistachalcone B (<b>2</b>), pistaflavanone A (<b>3</b>), pistachalcone C (<b>4</b>), and pistachalcone D (<b>5</b>) were elucidated by the analysis of spectroscopic data. The known compounds rhuschalcone II (<b>6</b>), rhuschalcone VI (<b>7</b>), and pauferrol B (<b>8</b>) were also isolated and identified. Our <i>in vitro</i> analysis found that compounds isolated from <i>P. weinmannifolia</i> root extract exert anti-inflammatory effects in phorbol myristate acetate (PMA)-induced NCI-H292 airway epithelial cells by the suppression of expression levels such as interleukin-8 (IL-8) and mucin 5AC (MUC5AC), which are closely related to the pulmonary inflammatory response in the pathogenesis of COPD. Therefore, these dihydrochalcone derivatives may have value as new starting materials for the development of drug candidates against COPD.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389510","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 : 2025-02-10DOI: 10.1021/acs.jnatprod.4c00911
Bailey A Bell, Josephine M Anderson, Scott R Rajski, Tim S Bugni
Metal chelating small molecules (metallophores) play significant roles in microbial interactions and bacterial survival; however, current methods to identify metallophores are limited by low sensitivity, a lack of metal selectivity, and/or complicated data analysis. To overcome these limitations, we developed a novel approach for detecting metallophores in natural product extracts using ion mobility-coupled mass spectrometry (IM-MS). As a proof of concept, marine bacterial extracts containing known metallophores were analyzed by IM-MS with and without added metals, and the data were compared between conditions to identify metal-binding metabolites. Ions with changes in both mass and mobility were specific to metallophores, enabling their identification within these complex extracts. Additionally, we compared the use of direct infusion (DI) and liquid chromatography (LC) separation with IM-MS. For most samples, DI outperformed LC by minimizing the time required for data collection and simplifying analysis. However, for some samples, LC improved the detection of metallophores likely by reducing ion suppression. IM-MS was then used to identify 10 metallophores in an extract from a marine Micromonospora sp. Overall, incorporating IM-MS facilitated the rapid detection of metal-binding natural products in complex bacterial extracts through the comparison of mass and mobility data in the presence and absence of metals.
{"title":"Ion Mobility-Coupled Mass Spectrometry for Metallophore Detection.","authors":"Bailey A Bell, Josephine M Anderson, Scott R Rajski, Tim S Bugni","doi":"10.1021/acs.jnatprod.4c00911","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00911","url":null,"abstract":"<p><p>Metal chelating small molecules (metallophores) play significant roles in microbial interactions and bacterial survival; however, current methods to identify metallophores are limited by low sensitivity, a lack of metal selectivity, and/or complicated data analysis. To overcome these limitations, we developed a novel approach for detecting metallophores in natural product extracts using ion mobility-coupled mass spectrometry (IM-MS). As a proof of concept, marine bacterial extracts containing known metallophores were analyzed by IM-MS with and without added metals, and the data were compared between conditions to identify metal-binding metabolites. Ions with changes in both mass and mobility were specific to metallophores, enabling their identification within these complex extracts. Additionally, we compared the use of direct infusion (DI) and liquid chromatography (LC) separation with IM-MS. For most samples, DI outperformed LC by minimizing the time required for data collection and simplifying analysis. However, for some samples, LC improved the detection of metallophores likely by reducing ion suppression. IM-MS was then used to identify 10 metallophores in an extract from a marine <i>Micromonospora</i> sp. Overall, incorporating IM-MS facilitated the rapid detection of metal-binding natural products in complex bacterial extracts through the comparison of mass and mobility data in the presence and absence of metals.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389512","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 : 2025-02-07DOI: 10.1021/acs.jnatprod.4c01327
Sravya Surendran, Chandrendu K C, Goreti Rajendar
The first enantioselective total synthesis and structure revision of isolophanthin E and syntheses of proposed structures of isolophanthins A, B, and C are demonstrated. Natural product 3β-hydroxy-8,11,13,15-abietatetraene was directly synthesized utilizing an efficient cationic polyene cyclization, and it is used as a common intermediate in the synthesis of isolophanthins and related abietatriene natural products. Two distinct synthetic routes were established for the synthesis of different stereoisomers of isolophanthin E. Spectroscopic analysis and structural assignment of isolophanthin E stereoisomers provide valuable insights into the relative configuration of the C-2, C-3-dihydroxy A ring of similar terpenoids, aiding in the identification of their configuration. A total of seven diterpenoids were obtained using regioselective chloromethylation, Sharpless dihydroxylation, Cu(II) catalyzed allyl-benzyl coupling, epoxide-initiated polyene cyclization, Rubottom oxidation, and additive-controlled dihydroxylation as key synthetic steps.
{"title":"An Enantioselective Approach for the Structure Revision of Isolophanthin E and Syntheses of Proposed Structures of Isolophanthins A, B, and C.","authors":"Sravya Surendran, Chandrendu K C, Goreti Rajendar","doi":"10.1021/acs.jnatprod.4c01327","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01327","url":null,"abstract":"<p><p>The first enantioselective total synthesis and structure revision of isolophanthin E and syntheses of proposed structures of isolophanthins A, B, and C are demonstrated. Natural product 3β-hydroxy-8,11,13,15-abietatetraene was directly synthesized utilizing an efficient cationic polyene cyclization, and it is used as a common intermediate in the synthesis of isolophanthins and related abietatriene natural products. Two distinct synthetic routes were established for the synthesis of different stereoisomers of isolophanthin E. Spectroscopic analysis and structural assignment of isolophanthin E stereoisomers provide valuable insights into the relative configuration of the C-2, C-3-dihydroxy A ring of similar terpenoids, aiding in the identification of their configuration. A total of seven diterpenoids were obtained using regioselective chloromethylation, Sharpless dihydroxylation, Cu(II) catalyzed allyl-benzyl coupling, epoxide-initiated polyene cyclization, Rubottom oxidation, and additive-controlled dihydroxylation as key synthetic steps.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363167","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 : 2025-02-07DOI: 10.1021/acs.jnatprod.4c01321
Brodie W Bulcock, Yit-Heng Chooi, Gavin R Flematti
Quantum chemical spectroscopic calculations have grown increasingly popular in natural products research for aiding the elucidation of chemical structures, especially their stereochemical configurations. These calculations have become faster with modern computational speeds, but subsequent data handling, inspection, and presentation remain key bottlenecks for many researchers. In this article, we introduce the SpectroIBIS computer program as a user-friendly tool to automate tedious tasks commonly encountered in this workflow. Through a simple graphical user interface, researchers can drag and drop Gaussian or ORCA output files to produce Boltzmann-averaged ECD, VCD, UV-vis and IR data, optical rotations, and/or 1H and 13C NMR chemical shifts in seconds. Also produced are formatted, publication-quality supplementary data tables containing conformer energies and atomic coordinates, saved to a DOCX file compatible with Microsoft Word and LibreOffice. Importantly, SpectroIBIS can assist researchers in finding common calculation issues by automatically checking for redundant conformers and imaginary frequencies. Additional useful features include recognition of conformer energy recalculations at a higher theory level, and automated generation of input files for quantum chemistry programs with optional exclusion of high-energy conformers. Lastly, we demonstrate the applicability of SpectroIBIS with spectroscopic calculations for five natural products. SpectroIBIS is open-source software available as a free desktop application (https://github.com/bbulcock/SpectroIBIS).
{"title":"SpectroIBIS: Automated Data Processing for Multiconformer Quantum Chemical Spectroscopic Calculations.","authors":"Brodie W Bulcock, Yit-Heng Chooi, Gavin R Flematti","doi":"10.1021/acs.jnatprod.4c01321","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01321","url":null,"abstract":"<p><p>Quantum chemical spectroscopic calculations have grown increasingly popular in natural products research for aiding the elucidation of chemical structures, especially their stereochemical configurations. These calculations have become faster with modern computational speeds, but subsequent data handling, inspection, and presentation remain key bottlenecks for many researchers. In this article, we introduce the SpectroIBIS computer program as a user-friendly tool to automate tedious tasks commonly encountered in this workflow. Through a simple graphical user interface, researchers can drag and drop Gaussian or ORCA output files to produce Boltzmann-averaged ECD, VCD, UV-vis and IR data, optical rotations, and/or <sup>1</sup>H and <sup>13</sup>C NMR chemical shifts in seconds. Also produced are formatted, publication-quality supplementary data tables containing conformer energies and atomic coordinates, saved to a DOCX file compatible with Microsoft Word and LibreOffice. Importantly, SpectroIBIS can assist researchers in finding common calculation issues by automatically checking for redundant conformers and imaginary frequencies. Additional useful features include recognition of conformer energy recalculations at a higher theory level, and automated generation of input files for quantum chemistry programs with optional exclusion of high-energy conformers. Lastly, we demonstrate the applicability of SpectroIBIS with spectroscopic calculations for five natural products. SpectroIBIS is open-source software available as a free desktop application (https://github.com/bbulcock/SpectroIBIS).</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363172","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}