Journal of Natural Products 最新文献_第5页

Semi-Synthesis of Dimeric Cannabidiol Derivatives and Evaluation of their Affinity at Neurological Targets.

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-01-24 DOI: 10.1021/acs.jnatprod.4c01174

Zachary Stryker, Jorge I Castillo-Arellano, Stephen J Cutler, Michael D Wyatt, Francisco León

{"title":"Semi-Synthesis of Dimeric Cannabidiol Derivatives and Evaluation of their Affinity at Neurological Targets.","authors":"Zachary Stryker, Jorge I Castillo-Arellano, Stephen J Cutler, Michael D Wyatt, Francisco León","doi":"10.1021/acs.jnatprod.4c01174","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01174","url":null,"abstract":"Cannabidiol (CBD) is a natural product associated with a wide range of biological and therapeutic activities. Despite the widespread cultural acceptance of CBD as a medicinal agent, much remains to be determined regarding its precise mechanism(s) of action in treating multiple conditions. CBD has been shown to promiscuously interact with several neurological targets with varying affinities. To expand the chemical space of phytocannabinoids and develop novel chemical compounds, we have designed and synthesized a series of CBD and Δ8-THC homodimers, and CBD/Δ8-THC heterodimers. The capacity of the dimers to interact with a panel of CNS targets was explored along with the capacity to activate CB1 receptors, as measured by a GIRK channel activation assay. In the panel screen, the dimers were shown to be generally more active toward 5-HT2B and sigma 2 receptors with a range of Ki values from 0.6 to 8.7 μM. These findings provide early evidence that this new class of dimers can serve as novel chemical entities to explore receptor function and the potential for these dimers to have bivalent, bitopic, or dual mechanisms of action.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031528","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}

引用次数: 0

Chromones Featuring a [6,6]-Spiroketal Moiety Produced by Coculture of the Endophytic Fungi Chaetomium virescens and Xylaria Grammica. 含有[6,6]-螺旋体片段的内生真菌绿毛毛菌和Grammica Xylaria共培养的色素

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-01-24 Epub Date: 2024-12-17 DOI: 10.1021/acs.jnatprod.4c00773

Sitian Zhang, Nanjing Ding, Xinyu Zheng, Yuling Lu, Jiangchun Wei, Hanxiao Zeng, Weiguang Sun, Yuan Zhou, Ya Gao, Yonghui Zhang, Zhengxi Hu

{"title":"Chromones Featuring a [6,6]-Spiroketal Moiety Produced by Coculture of the Endophytic Fungi Chaetomium virescens and Xylaria Grammica.","authors":"Sitian Zhang, Nanjing Ding, Xinyu Zheng, Yuling Lu, Jiangchun Wei, Hanxiao Zeng, Weiguang Sun, Yuan Zhou, Ya Gao, Yonghui Zhang, Zhengxi Hu","doi":"10.1021/acs.jnatprod.4c00773","DOIUrl":"10.1021/acs.jnatprod.4c00773","url":null,"abstract":"Under the guidance of HPLC-DAD analysis, ten new chromones featuring a rare [6,6]-spiroketal moiety, namely chaetovirexylariones A-J (1-10), together with two known congeners (11-12), were isolated from coculture of the endophytic fungi Chaetomium virescens and Xylaria grammica, from the rhizome of the medicinal plant Smilax glabra Roxb. Their structures were elucidated via a combination of NMR and HRESIMS data, and the absolute configurations of 1-10 were determined by the chemical conversion and single-crystal X-ray diffraction (Cu Kα) experiments, as well as the comparison of the experimental and calculated electronic circular dichroism (ECD) data. Compound 6 is the first report as a racemate of this type of natural product. Compound 10 represents the first example of a [6,6]-spiroketal chromone bearing a 5-amino-3-methyl-2-pentenoic acid fragment. Compound 8 demonstrated a reduction in PTX resistance of SW620/AD300 by a factor of 45, and had the potential to be an effective P-gp inhibitor and an antitumor chemotherapy sensitizer.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"36-48"},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833102","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}

引用次数: 0

Metabologenomics-Driven Discovery of Nocardimicins from a Psychrophilic Nocardia sp. Strain. 代谢基因组学驱动的嗜冷诺卡菌菌株诺卡霉素的发现。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-01-24 Epub Date: 2024-12-20 DOI: 10.1021/acs.jnatprod.4c01140

Suling Xu, Nengfei Wang, Qingzhou Meng, Wenjie Ma, Huayue Li

引用次数: 0

Neuromodulating Alkaloids from Millipede Defensive Secretions.

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-01-24 Epub Date: 2024-12-30 DOI: 10.1021/acs.jnatprod.4c01162

Carla Menegatti, Jared S Wood, Paige Banks, Kenneth Knott, Jonathan S Briganti, Anthony J Briganti, Samuel V G McNally, Paul E Marek, Anne M Brown, Tappey H Jones, R Thomas Williamson, Emily Mevers

{"title":"Neuromodulating Alkaloids from Millipede Defensive Secretions.","authors":"Carla Menegatti, Jared S Wood, Paige Banks, Kenneth Knott, Jonathan S Briganti, Anthony J Briganti, Samuel V G McNally, Paul E Marek, Anne M Brown, Tappey H Jones, R Thomas Williamson, Emily Mevers","doi":"10.1021/acs.jnatprod.4c01162","DOIUrl":"10.1021/acs.jnatprod.4c01162","url":null,"abstract":"Millipedes have long been known to produce structurally diverse chemical defenses, including hydrogen cyanide, terpenoid alkaloids, and oxidized aromatics. Although the hydrogen cyanide and oxidized aromatic producing millipedes have been well studied, less than 10% of the terpenoid alkaloid producers have been chemically investigated. Several previous studies have shown that alkaloids disorient predators, but their biochemical target is currently unknown. Herein, we investigated the defensive secretions of a colobognath millipede, Ischnocybe plicata, and elucidated the constitution, absolute configuration, and conformation of four new highly oxidized terpenoid alkaloids, termed ischnocybines, using a range of analytical techniques. The ischnocybines are actively secreted from the defensive glands and were shown to disorient ants, a likely common predator. Evaluation of the ischnocybines in a panel of neuroreceptors revealed that ischnocybine A possesses potent (Ki 13.6 nM) and selective (100-fold) binding affinity for sigma-1, an orphan neuroreceptor, over sigma-2. These molecules represent the most complex alkaloids to be discovered from millipedes and provide the first potential insights into a biochemical target responsible for their defensive properties.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 1","pages":"110-118"},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027462","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}

引用次数: 0

Identification of a Biosynthetic Gene Cluster for the Production of the Blue-Green Pigment Xylindein by the Fungus Chlorociboria aeruginascens.

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-01-23 DOI: 10.1021/acs.jnatprod.4c00350

Yanfang Guo, Jorge Navarro-Muñoz, Caroline Rodenbach, Elske Dwars, Chendo Dieleman, Bart van den Hout, Bazante Sanders, Miaomiao Zhou, Ayodele Arogunjo, Russell J Cox, Arnold J M Driessen, Jérôme Collemare

{"title":"Identification of a Biosynthetic Gene Cluster for the Production of the Blue-Green Pigment Xylindein by the Fungus Chlorociboria aeruginascens.","authors":"Yanfang Guo, Jorge Navarro-Muñoz, Caroline Rodenbach, Elske Dwars, Chendo Dieleman, Bart van den Hout, Bazante Sanders, Miaomiao Zhou, Ayodele Arogunjo, Russell J Cox, Arnold J M Driessen, Jérôme Collemare","doi":"10.1021/acs.jnatprod.4c00350","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00350","url":null,"abstract":"Xylindein is a blue-green pigment produced by the fungi Chlorociboria aeruginascens and Chlorociboria aeruginosa. Its stunning color and optoelectronic properties make xylindein valuable for textiles and as a natural semiconductor material. However, producing xylindein from culture broths remains challenging because of the slow growth of the Chlorociboria species and the poor solubility of xylindein in organic solvents. An alternative production route for obtaining pure xylindein is heterologous expression of the xylindein biosynthetic genes. Here, we resequenced the genome of C. aeruginascens and C. aeruginosa, and subsequent genome mining and phylogenetic dereplication identified a unique candidate biosynthetic gene cluster with a nonreducing polyketide synthase (nrPKS). RNA sequencing during xylindein production revealed that the core gene XLNpks is co-regulated with eight other genes at the locus. Among those, XLNfas1 and XLNfas2 encode a putative fatty acid synthase, which likely provides the starter unit to XLNpks. Attempts to heterologously express in Aspergillus oryzae XLNpks alone or in combination with XLNfas1 and XLNfas2 did not yield any intermediate, but expression of the closely related viriditoxin nrPKS (VdtA) produced the expected intermediate. Based on our results, we propose a biosynthetic route to xylindein and suggest that the obtained A. oryzae transformants open ways to further study xylindein biosynthesis.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021321","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}

引用次数: 0

Synthesis and Chemical Structure of the Cyclic Heptapeptide Stylissamide H. 环七肽花蓟胺H的合成及化学结构。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-01-21 DOI: 10.1021/acs.jnatprod.4c01224

Yitong Li, Seren Osanai, Kenta Nakajima, Fusheng Xu, Hinata Sano, Hiroki Sato, Hiroshi Katagiri, Hiroyuki Konno

引用次数: 0

Isolation of Antiplasmodial Oxazoles and Isoflavonoids from the Roots of Oxytropis trichophysa and Total Synthesis of Oxazole-type Alkaloids. 毛棘棘豆根抗疟原虫恶唑类和异黄酮的分离及恶唑类生物碱的全合成。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-01-18 DOI: 10.1021/acs.jnatprod.4c01254

Buyanmandakh Buyankhishig, Toshihiro Murata, Koichi Narita, Chinbat Delgermaa, Yoshifumi Nishikawa, Nanang R Ariefta, Baasandorj Gantumur, Tseesuren Byambajav, Yoshinobu Ishikawa, Bekh-Ochir Davaapurev, Kenroh Sasaki, Javzan Batkhuu

{"title":"Isolation of Antiplasmodial Oxazoles and Isoflavonoids from the Roots of Oxytropis trichophysa and Total Synthesis of Oxazole-type Alkaloids.","authors":"Buyanmandakh Buyankhishig, Toshihiro Murata, Koichi Narita, Chinbat Delgermaa, Yoshifumi Nishikawa, Nanang R Ariefta, Baasandorj Gantumur, Tseesuren Byambajav, Yoshinobu Ishikawa, Bekh-Ochir Davaapurev, Kenroh Sasaki, Javzan Batkhuu","doi":"10.1021/acs.jnatprod.4c01254","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01254","url":null,"abstract":"A chemical examination of a root extract of Oxytropis trichophysa led to the isolation and identification of 23 compounds, including oxazole-type alkaloids and isoflavonoid derivatives. Notably, three oxazole-type alkaloids (1, 2, and 3) and two isoflavonoid derivatives (7 and 10) were obtained from a natural source for the first time. In addition, O. trichophysa derived 2,5-diphenyloxazoles and their derivatives were synthesized. Despite their potential activity, the antiplasmodial activities of naturally occurring 2,5-diphenyloxazoles and certain isoflavonoids remain unexplored. Therefore, the antiplasmodial activities of both the naturally occurring and synthesized compounds were evaluated against Plasmodium falciparum strain 3D7. Among the tested compounds, three naturally occurring oxazole-type alkaloids (1, 5, and 6), one synthesized alkaloid (34), and two isoflavonoid derivatives (13 and 15) demonstrated significant inhibitory effects, with half-maximal inhibitory concentration (IC50) values ranging from 3.1 to 6.2 μM and selective indices between 0.9 and 18.8. Compound 1 showed the most potent inhibitory activity, with an IC50 of 3.1 μM, while its cytotoxic concentration 50% value against human foreskin fibroblasts was found to be 8.5 μM. The oxazole-type alkaloids and isoflavonoids isolated from this plant provide valuable insights into its chemical composition and may help elucidate the antiplasmodial properties of O. trichophysa.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996168","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}

引用次数: 0

Screening, Discovery, and Optimization of the Natural Antitubercular Chlorflavonin from a Marine-Derived Fungal Library. 从海洋真菌文库中筛选、发现和优化天然抗结核氯黄酮。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-01-15 DOI: 10.1021/acs.jnatprod.4c01374

Cui-Fang Wang, Wen-Hui Wang, Ying Xu, Qun Zhang, Mei-Yan Wei, Yu-Cheng Gu, Tong-Yi Xu, Chang-Lun Shao

引用次数: 0

An Unexpected Activity of a Minor Cannabinoid: Cannabicyclol (CBL) Is a Potent Positive Allosteric Modulator of Serotonin 5-HT1A Receptor

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-01-15 DOI: 10.1021/acs.jnatprod.4c0097710.1021/acs.jnatprod.4c00977

Mehdi Haghdoost, Yvonne DePorre, Max Figi, Scott Young, Caitlyn Krebs and Marcel O. Bonn-Miller*,

{"title":"An Unexpected Activity of a Minor Cannabinoid: Cannabicyclol (CBL) Is a Potent Positive Allosteric Modulator of Serotonin 5-HT1A Receptor","authors":"Mehdi Haghdoost, Yvonne DePorre, Max Figi, Scott Young, Caitlyn Krebs and Marcel O. Bonn-Miller*, ","doi":"10.1021/acs.jnatprod.4c0097710.1021/acs.jnatprod.4c00977","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00977https://doi.org/10.1021/acs.jnatprod.4c00977","url":null,"abstract":"Cannabicyclol ((±)-CBL), a minor phytocannabinoid, is largely unexplored, with its biological activity previously undocumented. We studied its conversion from cannabichromene (CBC) using various acidic catalysts. Montmorillonite (K30) in chloroform at room temperature had the highest yield (60%) with minimal byproducts. Key reaction conditions, such as solvent, temperature, and time, significantly impacted the yield. The structure of (±)-CBL was confirmed via X-ray crystallography. Stability studies showed that (±)-CBL and its MCT oil dilution remain stable at 25–40 °C for three months. Radioligand binding assays revealed high affinity of CBL for the 5-HT1A receptor but weak interaction with CB1 and CB2 receptors. At 10 μM and 1 μM, (±)-CBL inhibited [3H]-8-hydroxy-DPAT binding to 5-HT1A by 75% and 20%, respectively. Functional assays showed that (±)-CBL acts as a weak agonist at high concentrations but a potent positive allosteric modulator of serotonin-induced activation at low concentrations. At 4 μM, (±)-CBL increased serotonin-induced β-arrestin recruitment from 20% to 80%. This unique modulatory profile highlights the potential of (±)-CBL in drug discovery targeting serotonin receptors.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 1","pages":"58–66 58–66"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143088218","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}

引用次数: 0

Heterologous Expression and Characterization of Estercin A, a Class II Lanthipeptide Derived from Clostridium estertheticum CF016, with Antimicrobial Activity against Clinically Relevant Pathogens. 对临床相关病原菌具有抑菌活性的酯酸梭菌CF016ⅱ类硫肽Estercin A的异源表达及特性研究

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-01-15 DOI: 10.1021/acs.jnatprod.4c00814

Chenhui Wang, Joseph Wambui, Maria Victoria Fernandez-Cantos, Simon Jurt, Jaap Broos, Roger Stephan, Oscar P Kuipers

{"title":"Heterologous Expression and Characterization of Estercin A, a Class II Lanthipeptide Derived from Clostridium estertheticum CF016, with Antimicrobial Activity against Clinically Relevant Pathogens.","authors":"Chenhui Wang, Joseph Wambui, Maria Victoria Fernandez-Cantos, Simon Jurt, Jaap Broos, Roger Stephan, Oscar P Kuipers","doi":"10.1021/acs.jnatprod.4c00814","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00814","url":null,"abstract":"Recent genome mining work revealed that unexplored habitats exhibit great potential for discovering new nonribosomal peptides (NRPs) and ribosomally synthesized and post-translationally modified peptides (RiPPs). Lanthipeptides are a group of RiPPs exhibiting a variety of biological functions. They are characterized by the presence of the thioether-containing bis-amino acids lanthionine and/or methyllanthionine. In this study, we heterologously expressed and structurally characterized estercin A, an unprecedented class II lanthipeptide derived from Clostridium estertheticum CF016 in Escherichia coli. Comprising 27 amino acids, estercin A features three overlapping (methyl-)lanthionine rings, with a shorter C-terminal part compared to most reported class II lanthipeptides. Estercin A exhibited selective antimicrobial properties against methicillin-resistant Staphylococcus aureus, bowel infection-associated Clostridium perfringens and Clostridium tetani. The mode of action of estercin A was determined as binding to lipid II on the cell membrane. Estercin A exhibited stability across a range of pH values and temperatures and showed resistance to degradation by trypsin. Our findings highlight estercin A as a novel and stable antimicrobial peptide with significant potential in combating clinically relevant pathogens.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996234","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}

引用次数: 0