Journal of Natural Products 最新文献

{"title":"Alstolarsines A–E, Indoline Alkaloids with Two Different Carbon Skeletons from Alstonia scholaris","authors":"Xu-Xin Zhu,&nbsp;Yao-Yue Fan,&nbsp;Cheng-Yu Zheng,&nbsp;Hong-Ying Yang,&nbsp;Kun Gao* and Jian-Min Yue*,&nbsp;","doi":"10.1021/acs.jnatprod.5c0002710.1021/acs.jnatprod.5c00027","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00027https://doi.org/10.1021/acs.jnatprod.5c00027","url":null,"abstract":"<p >Five complex indoline alkaloids, alstolarsines A–E (<b>1</b>–<b>5</b>) possessing two unprecedented carbon skeletons of 6/5/5/7/6/6(5) fused polycyclic systems, were isolated from <i>Alstonia scholaris</i>. Their structures were characterized using various methods including spectroscopic data, ECD spectra, and single-crystal X-ray diffraction. The inhibitory activities of alstolarsines A–D (<b>1</b>–<b>4</b>) on DRAK2 phosphorylation and ATP-citrate lyase were evaluated, but all of them were inactive.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 3","pages":"815–820 815–820"},"PeriodicalIF":3.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714165","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}

{"title":"Niacin Ester Derivative of Brefeldin A as a Potential Dual-Target Arf1/BMX Inhibitor for Bladder Cancer","authors":"Jian-Yu Liu,&nbsp;Yi-Jing Song,&nbsp;Peng-Jie Li,&nbsp;Yang Gao,&nbsp;Mei-Yan Wei and Chang-Lun Shao*,&nbsp;","doi":"10.1021/acs.jnatprod.5c0008610.1021/acs.jnatprod.5c00086","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00086https://doi.org/10.1021/acs.jnatprod.5c00086","url":null,"abstract":"<p >Bladder cancer is a common malignancy known for its high recurrence rate and poor survival rate. New strategies are urgently needed to reduce recurrence and improve prognosis. Arf1 and BMX are potential targets associated with the prognosis of bladder cancer. In this study, niacin ester derivatives of brefeldin A were synthesized by introducing nicotinic acid moieties at the 4-OH and 7-OH positions. Notably, the 4-monoester derivative, CHNQD-01228 (<b>2</b>), could significantly inhibit the proliferation of T24 cells (IC₅₀ = 0.22 μM) in a time-dependent manner. Furthermore, it dose-dependently inhibited T24 cell migration and colony formation, induced G1 phase arrest, and triggered apoptosis. Based on molecular modeling, CHNQD-01228 was evaluated to exhibit high binding affinity toward both Arf1 and BMX proteins. Further verification was conducted using cellular thermal shift assays and drug affinity responsive target stability assays. It suppressed the AKT/p-AKT and STAT3/p-STAT3 signaling pathways by targeting BMX in T24 cells, eliminated bladder cancer stem cells, and activated antitumor immunity via Arf1 inhibition. <i>In vivo</i> data further demonstrated that the dual-target inhibitor exhibited a potential antitumor efficacy against MB49 allograft tumors (TGI = 51.0%) and thus represents a promising therapeutic strategy for bladder cancer.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 3","pages":"830–841 830–841"},"PeriodicalIF":3.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714164","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}

{"title":"Total Syntheses, Absolute Configuration, and Cytotoxicity Evaluation of Ugonins L, S, U, and Z from the Rhizomes of Helminthostachys zeylanica","authors":"Cheng-Tin Lin,&nbsp;Jing-Jy Cheng,&nbsp;Huei-Ling You,&nbsp;Cheng-Hsun Hsieh,&nbsp;Chiao-Jou Pan and Ming-Jaw Don*,&nbsp;","doi":"10.1021/acs.jnatprod.4c0148710.1021/acs.jnatprod.4c01487","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01487https://doi.org/10.1021/acs.jnatprod.4c01487","url":null,"abstract":"<p >This study describes the first and efficient syntheses of naturally occurring ugonins L (<b>1a</b>), S (<b>2a</b>, <b>2b</b>), U (<b>3</b>), and Z (<b>4</b>). Naturally occurring ugonin S has two stereoisomers. On the basis of their NMR and specific rotation data, the absolute configuration of <i>trans</i>-ugonin L (<b>1a</b>) was determined as 10<i>R</i>,11<i>R</i>, while the absolute configurations of <i>trans</i>-ugonin S (<b>2a</b>) and <i>cis</i>-ugonin S (<b>2b</b>) were determined to be 10<i>R</i>,11<i>R</i> and 10<i>R</i>,11<i>S</i>, respectively. The naturally occurring <i>cis</i>-ugonin U (<b>3</b>) presented the 10<i>S</i>,11<i>R</i> configuration. The naturally occurring <i>cis</i>-ugonin Z (<b>4</b>) was suggested to have a 10<i>S</i>,11<i>R</i> configuration. Four isomers of compound <b>2</b> and two isomers of compound <b>3</b> showed moderate cytotoxic activities against the CEM and H460 human cancer cell lines.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 3","pages":"785–796 785–796"},"PeriodicalIF":3.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714090","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}

{"title":"Curvisetone─A Male-Specific Tricyclic nor-Diterpenoid from the Springtail Sinella curviseta","authors":"Anton Möllerke,&nbsp; and ,&nbsp;Stefan Schulz*,&nbsp;","doi":"10.1021/acs.jnatprod.4c0143210.1021/acs.jnatprod.4c01432","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01432https://doi.org/10.1021/acs.jnatprod.4c01432","url":null,"abstract":"<p >The structure determination and occurrence of curvisetone (<b>1</b>), a tricyclic nor-diterpenoid from the tiny Collembola <i>Sinella curviseta</i>, is reported. Utilizing NMR analysis and mass spectrometry, we identified curvisetone’s unique carbon skeleton and its occurrence in various sex and life stages. Curvisetone, carrying an unprecedented carbon tricyclic ring system, is an example of the distinct terpene usage of Collembola, which differentiates them from other arthropods.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 3","pages":"857–861 857–861"},"PeriodicalIF":3.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jnatprod.4c01432","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analgesic Grayanane-Derived Diterpenoids from the Flowers of Rhododendron molle","authors":"Yang Song,&nbsp;Hui-Min Yan,&nbsp;Bing Chai,&nbsp;Zhao-Xin Zhang,&nbsp;Fang-Fei Li,&nbsp;Qin-Yan Shi,&nbsp;Hai-Qiang Wang,&nbsp;Yong Li* and Shi-Shan Yu*,&nbsp;","doi":"10.1021/acs.jnatprod.4c0130310.1021/acs.jnatprod.4c01303","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01303https://doi.org/10.1021/acs.jnatprod.4c01303","url":null,"abstract":"<p >Ten new grayanane-derived diterpenoids, rhodomollein LVII–LXVI (<b>1</b>–<b>10</b>), along with the known compound rhodomollein XLIII (<b>11</b>), were isolated from the flowers of <i>Rhododendron molle</i>. Their structures were elucidated by detailed spectroscopic analysis, X-ray diffraction crystallography, and ECD calculations. Rhodomollein LVII–LIX (<b>1</b>–<b>3</b>) are the first-discovered 3-<i>O</i>-<i>(E)</i>-<i>p</i>-coumaroylquinic acid, nicotinic acid, and 2-furoic acid derivatives of grayanane diterpenoids, respectively. In an acetic acid-induced writhing test, compounds <b>1</b> and <b>3</b> demonstrated significant antinociceptive effects with writhing inhibition rates of 77.2% and 71.5%, respectively, at a dose of 0.2 mg/kg. Compound <b>1</b> was found to be twice as potent as morphine, exhibiting significantly lower toxicity (LD₅₀ = 130.90 mg/kg, i.p.) compared to rhodojaponin VI (LD₅₀ = 1.79 mg/kg, i.p.).</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 3","pages":"671–681 671–681"},"PeriodicalIF":3.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713920","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}

{"title":"Efficient and Selective Biosynthesis of a Precursor-Directed FK506 Analogue: Paving the Way for Click Chemistry","authors":"Dušan Goranovič,&nbsp;Branko Jenko,&nbsp;Barbara Ramšak,&nbsp;Ajda Podgoršek Berke,&nbsp;Leon Bedrač,&nbsp;Jaka Horvat,&nbsp;Martin Šala,&nbsp;Damjan Makuc,&nbsp;Guilhermina M. Carriche,&nbsp;Luana Silva,&nbsp;Aleksandra Lopez Krol,&nbsp;Alen Pšeničnik,&nbsp;María Beatriz Durán Alonso,&nbsp;Martina Avbelj,&nbsp;Stojan Stavber,&nbsp;Janez Plavec,&nbsp;Tim Sparwasser,&nbsp;Rolf Müller,&nbsp;Gregor Kosec,&nbsp;Štefan Fujs and Hrvoje Petković*,&nbsp;","doi":"10.1021/acs.jnatprod.4c0039410.1021/acs.jnatprod.4c00394","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00394https://doi.org/10.1021/acs.jnatprod.4c00394","url":null,"abstract":"<p >The medically important immunosuppressant FK506 is a structurally complex macrolactone biosynthesized by a combined polyketide synthase and a nonribosomal peptide synthetase enzyme complex. Its acyltransferase domain 4 (AT4) selects an unusual extender unit, resulting in an allyl moiety on carbon 21 of the macrolactone backbone. Based on the AT4 domain, chemobiosynthetic processes have been developed that enable the introduction of diverse moieties at the carbon 21 position. However, the novel moieties that were introduced into the polyketide backbone are chemically inert. Reported here is a novel and efficient chemobiosynthetic approach that ensures high titer of an FK506 analogue containing a propargyl moiety. The novel FK506 analogue displays lower immunosuppression activity than FK506 with significantly reduced cytotoxicity. More importantly, the propargyl moiety contains a terminal alkyl group, which makes click chemistry reactions possible; this approach may potentially be translated to other medically important drugs of polyketide origin.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 3","pages":"619–630 619–630"},"PeriodicalIF":3.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jnatprod.4c00394","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Total Synthesis of (−)- and (+)-Talaroenamine B and Diphenylene Derivatives","authors":"Zhenzhen Zhang,&nbsp;Wei Li,&nbsp;Miaomiao Chai,&nbsp;Bing Wang,&nbsp;Xiaomin Zhang,&nbsp;Dehai Li,&nbsp;Xueqian He* and Zhenhui Wang*,&nbsp;","doi":"10.1021/acs.jnatprod.5c0014410.1021/acs.jnatprod.5c00144","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00144https://doi.org/10.1021/acs.jnatprod.5c00144","url":null,"abstract":"<p >The first total synthesis of (±)-talaroenamine B was achieved through a concise four-step procedure. The key feature of this synthetic strategy lies in a one-pot reaction involving I (III)-mediated oxidative dearomatization to construct a racemic cyclohexanedione unit, followed by imination using a chiral auxiliary to afford a separable mixture of diastereoisomers. A further acid-catalyzed substitution reaction of aniline with the diastereoisomers led to the natural product (−)-talaroenamine B and its enantiomer (+)-talaroenamine B. Additionally, virtual screening was utilized to expand the chemo-diversity of talaroenamines, and (±)-talaroenamine B diphenylene derivatives <b>6</b>–<b>11</b> were obtained by replacing aniline with selected aniline derivatives in the final step of synthesis. The structures of the synthetic compounds were elucidated using NMR, HRESIMS, and electronic circular dichroism (ECD) data. Compound <b>6b</b> displayed an acetylcholinesterase (AChE) inhibitory effect with an IC₅₀ value of 4.5 μM, as well as cytotoxicity against the K562 cell line with an IC₅₀ value of 5.6 μM.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 3","pages":"842–849 842–849"},"PeriodicalIF":3.3,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713849","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}

{"title":"Connecting the Practice of Modern Qualitative and Quantitative NMR Analysis with Its Theoretical Foundation","authors":"Lucy Botros,&nbsp;Yang Liu*,&nbsp;Charlotte Corbett,&nbsp;Dan Sørensen,&nbsp;Christina Szabo,&nbsp;Anton Bzhelyansky,&nbsp;Matthias Niemitz,&nbsp;Petrus Korhonen,&nbsp;Guido F. Pauli,&nbsp;Patrick Giraudeau and G. Joseph Ray*,&nbsp;","doi":"10.1021/acs.jnatprod.4c0101310.1021/acs.jnatprod.4c01013","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01013https://doi.org/10.1021/acs.jnatprod.4c01013","url":null,"abstract":"<p >This Perspective seeks to reconnect the current practice of nuclear magnetic resonance (NMR) spectroscopy in chemical structure and quantitative (qNMR) analysis with its roots in classical physics and quantum mechanics (QM). Rationales for this approach are derived from various angles, including focused reviews of the key parameters of the nuclear resonance phenomenon, the structural information richness of NMR spectra, and significant progress in both computational and spectrometer hardware. This provides collective reasoning for the reintegration of computational quantum mechanical spectral analysis (QMSA) into the contemporary practice of NMR spectral interpretation. Retethering operator-dependent visual <i>phenotypic</i> with QM-driven computational <i>genotypic</i> analysis yields more objective and accurate information by taking advantage of QM as the foundational reference point for NMR. Powerful computational tools for compound <i>genotyping</i> are available and evolve rapidly toward automation. In addition to enhancing the rigor and reproducibility of structure elucidation of new and the dereplication of known compounds, QM anchoring enables competent resolution of peak overlap, with resulting benefits in qNMR and low-field/benchtop NMR analysis. Furthermore, examination of common definitions and documentation practices shows that an evolutionary reconciliation of NMR terminology helps resolve ambiguities: shifting from <i>phenotypic</i> peak focus to <i>genotypic</i> QM-based pattern analysis is not only the logical next step when communicating structures of natural products and other molecules reproducibly but also a timely approach, as it yields QMSA-verified data for evolving knowledge bases for molecules of biomedical relevance.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 3","pages":"877–888 877–888"},"PeriodicalIF":3.3,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jnatprod.4c01013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ingenane Diterpenoids from Euphorbia peplus as Potential New CHK1 Inhibitors That Sensitize Cancer Cells to Chemotherapy","authors":"Mi Zhou,&nbsp;Yanlan Yang,&nbsp;Shoulun He,&nbsp;Qiannan Xu,&nbsp;Chunchun Du,&nbsp;Wenjing Tian* and Haifeng Chen*,&nbsp;","doi":"10.1021/acs.jnatprod.4c0134310.1021/acs.jnatprod.4c01343","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01343https://doi.org/10.1021/acs.jnatprod.4c01343","url":null,"abstract":"<p >Phosphorylation of checkpoint kinase 1 at Ser-345 (p-CHK1(S345)) mediates the replication stress response in cancer cells, leading to chemotherapy resistance. Therefore, finding inhibitors of p-CHK1(S345) is currently a promising strategy to prevent acquired drug resistance. In this study, 14 ingenane diterpenoids (<b>1</b>–<b>14</b>), involving two undescribed compounds possessing an unprecedented exocyclic double bond Δ⁶⁽²⁰⁾, were identified from <i>Euphorbia peplus</i>. The inhibitory effects of the isolated compounds on p-CHK1(S345) and their structure–activity relationship (SAR) were investigated. Compounds <b>7</b> and <b>8</b> presented the strongest inhibitory effects, abrogated cell cycle arrest, and caused the accumulation of DNA damage, improving the sensitivity of cancer cells to chemotherapeutic drugs. An <i>in vivo</i> assay confirmed the enhancement of <b>8</b> on the anticancer effect of topotecan via blocking of p-CHK1(S345). Mechanistically, <b>8</b> increased CHK1 ubiquitination to inhibit p-CHK1(S345) via activation of protein kinase C (PKC). PKC activation was first found to enhance CHK1 ubiquitination to block p-CHK1(S345). Above all, this finding not only indicates that compound <b>8</b> could be developed as a novel CHK1 inhibitor but also reveals a previously unrecognized role of PKC in regulating cancer chemotherapy sensitivity.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 3","pages":"688–705 688–705"},"PeriodicalIF":3.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713886","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}

{"title":"Contignasterines, Anti-Inflammatory 2-Aminoimidazole Steroids from the Sponge <i>Neopetrosia</i> cf. <i>rava</i> Collected in the Bismarck Sea.","authors":"Juan Ortega-Vidal, Maggie M Reddy, Nadia Pérez-Fuentes, Rebeca Alvariño, Svenja Burth, Amparo Alfonso, Carmen Vale, Jorge R Virués-Segovia, Augustine Mungkaje, Luis M Botana, Olivier P Thomas","doi":"10.1021/acs.jnatprod.5c00118","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00118","url":null,"abstract":"<p><p>Sponges of the genus <i>Neopetrosia</i> are known for the production of a large diversity of bioactive metabolites. Contignasterines A (<b>1</b>) and B (<b>2</b>) were isolated as major metabolites of the sponge <i>Neopetrosia</i> cf. <i>rava</i> collected in the Bismarck Sea along with the known and highly bioactive steroid contignasterol (<b>3</b>) possessing a similar oxidized aglycone. Contignasterines are characterized by the presence of a 2-aminoimidazole branched on the side-chains of the oxidized steroid, and <b>1</b> also contains an unusual phosphate group at C-7. The anti-inflammatory activities of these compounds were investigated and revealed that all three compounds inhibited the production of pro-inflammatory mediators.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583944","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}