Journal of Natural Products 最新文献_第2页

An Unexpected Activity of a Minor Cannabinoid: Cannabicyclol (CBL) Is a Potent Positive Allosteric Modulator of Serotonin 5-HT_1A Receptor. 一种意想不到的小大麻素活性：大麻环醇（CBL）是5-羟色胺5-HT1A受体的一种有效的阳性变构调节剂。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-01-24 Epub Date: 2025-01-15 DOI: 10.1021/acs.jnatprod.4c00977

Mehdi Haghdoost, Yvonne DePorre, Max Figi, Scott Young, Caitlyn Krebs, 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, Marcel O Bonn-Miller","doi":"10.1021/acs.jnatprod.4c00977","DOIUrl":"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":" ","pages":"58-66"},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981966","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

Derivatization of Microcystins Can Increase Target Inhibition while Reducing Cellular Uptake. 微囊藻毒素的衍生物化可以增加对目标的抑制作用，同时减少细胞的吸收。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-01-24 Epub Date: 2024-10-20 DOI: 10.1021/acs.jnatprod.4c00688

Laura L Sallandt, Clemens A Wolf, Sabine Schuster, Heike Enke, Dan Enke, Gerhard Wolber, Timo H J Niedermeyer

{"title":"Derivatization of Microcystins Can Increase Target Inhibition while Reducing Cellular Uptake.","authors":"Laura L Sallandt, Clemens A Wolf, Sabine Schuster, Heike Enke, Dan Enke, Gerhard Wolber, Timo H J Niedermeyer","doi":"10.1021/acs.jnatprod.4c00688","DOIUrl":"10.1021/acs.jnatprod.4c00688","url":null,"abstract":"Microcystins, a large family of nonribosomal cyclic heptapeptides known for their hepatotoxicity, are among the best-studied cyanobacterial toxins. Recently, they have been discussed as leads for the development of anticancer drug substances. Their main mode-of-action is inhibition of the eukaryotic serine/threonine protein phosphatases 1 and 2A. Unlike many cytotoxins that can cross cell membranes by passive diffusion, microcystins depend on active uptake via organic anion transporting polypeptides 1B1 or 1B3. Both phosphatase inhibition and transportability strongly depend on the structure of the individual microcystin. Here, we present how chemical modification of positions 2 and 4 of the microcystin core structure can alter these two properties. Aiming to reduce transportability and increase phosphatase inhibition, we used pharmacophore modeling to investigate the phosphatase inhibition potential of microcystins derivatized with small molecules containing a variety of functional groups. The respective derivatives were synthesized using click chemistry. We discovered that some derivatized microcystins can address a yet undescribed subpocket of the protein phosphatase 1. The derivatized microcystins were tested for phosphatase 1 inhibition and cytotoxicity on transporter-expressing cell lines, revealing that target inhibition and transportability of microcystins can independently be influenced by the physicochemical properties, especially of the residue located in position 2 of the microcystin. Derivatization with small acids or amino acids resulted in microcystins with a favorable ratio of inhibition to transportability, making these derivatives potentially suitable for drug development.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"3-14"},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453368","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

Chemical Basis of the Traditional Ayurvedic Detoxification Process of the Toxic Medicinal Plant Plumbago zeylanica. 传统阿育吠陀解毒过程的化学基础。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-01-24 Epub Date: 2025-01-03 DOI: 10.1021/acs.jnatprod.3c00975

Ankur Kumar Tanwar, Debanjan Chatterjee, Neha Jain, Shivam Sharma, Kulbhushan Tikoo, Inder Pal Singh

{"title":"Chemical Basis of the Traditional Ayurvedic Detoxification Process of the Toxic Medicinal Plant Plumbago zeylanica.","authors":"Ankur Kumar Tanwar, Debanjan Chatterjee, Neha Jain, Shivam Sharma, Kulbhushan Tikoo, Inder Pal Singh","doi":"10.1021/acs.jnatprod.3c00975","DOIUrl":"10.1021/acs.jnatprod.3c00975","url":null,"abstract":"Certain medicinal plants utilized in the traditional ayurvedic system are poisonous when used raw, but are used following a detoxification process. The Ayurvedic Formulary of India (AFI) provides details about these detoxification (known as \"sodhana\") processes as per traditional procedures. This research endeavor aimed to uncover the fundamental principles underlying the detoxification approach applied to Plumbago zeylanica, commonly referred to as \"swet chitrak\", in which plumbagin is the primary toxic constituent. Both unprocessed and processed (detoxified) extracts as well as the detoxification media were subjected to analysis for secondary metabolites using different analytical techniques. This investigation revealed a reduction in plumbagin content, its conversion to epoxyplumbagin and zeylanone and a noteworthy decrease in cis- and trans-isoshinanolone during detoxification. Furthermore, it was confirmed that pure plumbagin when subjected to the same detoxification conditions, is partially converted into epoxyplumbagin, and that cis and trans-isoshinanolone showed interconversion. The current work establishes the chemical basis of the age-old traditional ayurvedic process of detoxification of P. zeylanica.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"15-23"},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925811","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

Isolation and Characterization of Insecticidal Cyclotides from Viola communis. 从 Viola communis 中分离和鉴定杀虫环苷。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-01-24 Epub Date: 2024-05-15 DOI: 10.1021/acs.jnatprod.4c00168

Negin Khatibi, Yen-Hua Huang, Conan K Wang, Thomas Durek, Edward K Gilding, David J Craik

{"title":"Isolation and Characterization of Insecticidal Cyclotides from Viola communis.","authors":"Negin Khatibi, Yen-Hua Huang, Conan K Wang, Thomas Durek, Edward K Gilding, David J Craik","doi":"10.1021/acs.jnatprod.4c00168","DOIUrl":"10.1021/acs.jnatprod.4c00168","url":null,"abstract":"Cyclotides are cysteine-rich plant-derived peptides composed of 28-37 amino acids with a head-to-tail cyclic backbone and a knotted arrangement of three conserved disulfide bonds. Their beneficial biophysical properties make them promising molecules for pharmaceutical and agricultural applications. The Violaceae plant family is the major cyclotide-producing family, and to date, every examined plant from this family has been found to contain cyclotides. The presence of cyclotides in Viola communis was inferred by mass spectroscopy previously, but their sequences and properties had yet to be explored. In this study, the occurrence of cyclotides in this plant was investigated using proteomics and transcriptomics. Twenty cyclotides were identified at the peptide level, including two new members from the bracelet (Vcom1) and Möbius (Vcom2) subfamilies. Structural analysis of these newly identified peptides demonstrated a similar fold compared with cyclotides from the same respective subfamilies. Biological assays of Vcom1 and Vcom2 revealed them to be cytotoxic to Sf9 insect cell lines, with Vcom1 demonstrating higher potency than Vcom2. The results suggest that they could be further explored as insecticidal agents and confirm earlier general findings that bracelet cyclotides have more potent insecticidal activity than their Möbius relatives. Seven new cyclotide-like sequences were observed in the transcriptome of V. communis, highlighting the Violaceae as a rich source for new cyclotides with potential insecticidal activity. An analysis of sequences flanking the cyclotide domain in the various precursors from V. communis and other Violaceae plants revealed new insights into cyclotide processing and suggested the possibility of two alternative classes of N-terminal processing enzymes for cyclotide biosynthesis.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"24-35"},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920306","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

Neuroprotective Indole Alkaloids from the Soil-Derived Fungus Trichocladium sp. XZ8. 土源真菌Trichocladium sp. XZ8中神经保护吲哚类生物碱。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-01-24 Epub Date: 2025-01-11 DOI: 10.1021/acs.jnatprod.4c01250

Xiao-Qi Duan, Xin-Yu Wang, Huai-Chang Qi, Yi-Jie Zhai, Wen-Bo Han

引用次数: 0

The Paradox of Antimalarial Terpenoid Isonitrile Biosynthesis Explained. Proposal of Cyanoformate as an NC Delivery Vector. 抗疟萜类异腈生物合成的悖论解释。氰甲酸酯作为NC载体的构想。

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.4c01295

Tadeusz F Molinski

引用次数: 0

Genome-informed Discovery of Monchicamides A-K: Cyanobactins from the Microcoleaceae Cyanobacterium LEGE 16532. 微甘蓝科蓝细菌LEGE 16532中Monchicamides A-K: Cyanobactins的基因组信息发现。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-01-24 Epub Date: 2024-12-24 DOI: 10.1021/acs.jnatprod.4c01063

Raquel Castelo-Branco, João P Pereira, Sara Freitas, Marco Preto, Ana R Vieira, João Morais, Pedro N Leão

{"title":"Genome-informed Discovery of Monchicamides A-K: Cyanobactins from the Microcoleaceae Cyanobacterium LEGE 16532.","authors":"Raquel Castelo-Branco, João P Pereira, Sara Freitas, Marco Preto, Ana R Vieira, João Morais, Pedro N Leão","doi":"10.1021/acs.jnatprod.4c01063","DOIUrl":"10.1021/acs.jnatprod.4c01063","url":null,"abstract":"Genome mining has emerged as an important tool for the discovery of natural products and is particularly effective for the swift identification of ribosomally synthesized and post-translationally modified peptides (RiPPs). Among RiPPs, cyanobactins have gained attention due to their diverse structures and bioactive properties. Here, we explored the Microcoleaceae cyanobacterium LEGE 16532 strain and identified the mon biosynthetic gene cluster (BGC), which was predicted to encode cyanobactin-like molecules. This led to the detection of 11 macrocyclic cyanobactins, the monchicamides, some of which feature mono- or diprenylation. One of the compounds was isolated, monchicamides I (9), and its planar structure was established by LC-HRESIMS/MS data as well as 1D and 2D NMR spectroscopy, confirming forward O-prenylation in Tyr. In addition, the absolute configuration of compound 9 was determined by Marfey's method and chiral-phase HPLC. The structures of the additional cyanobactins were proposed from MS/MS data analysis. The bioactivity profile of the isolated compound was also evaluated, but no cytotoxic, antimicrobial, or antiamoebic activity was observed.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"86-93"},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880690","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

Cytotoxic and Noncytotoxic Steroidal Constituents of Cryptolepis dubia. 隐藻的细胞毒性和非细胞毒性甾体成分。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-01-24 Epub Date: 2025-01-14 DOI: 10.1021/acs.jnatprod.4c01257

Yulin Ren, Elizabeth N Kaweesa, Ruoheng Zhou, Yue Liu, Kongmany Sydara, Mouachanh Xayvue, Djaja D Soejarto, Sijin Wu, Xiaolin Cheng, Joanna E Burdette, A Douglas Kinghorn

{"title":"Cytotoxic and Noncytotoxic Steroidal Constituents of Cryptolepis dubia.","authors":"Yulin Ren, Elizabeth N Kaweesa, Ruoheng Zhou, Yue Liu, Kongmany Sydara, Mouachanh Xayvue, Djaja D Soejarto, Sijin Wu, Xiaolin Cheng, Joanna E Burdette, A Douglas Kinghorn","doi":"10.1021/acs.jnatprod.4c01257","DOIUrl":"10.1021/acs.jnatprod.4c01257","url":null,"abstract":"(-)-Cryptanoside A (1) was identified previously as a major cytotoxic component of the stems of Cryptolepis dubia collected in Laos, which mediates its activity by targeting Na+/K+-ATPase (NKA), with hydrogen bonds formed between its 11- and 4'-hydroxy groups and NKA being observed in its docking profile. In a continuing investigation, 1 and its 17-epimer, (-)-17-epi-cryptanoside A (2), and the new (+)-2-hydroxyandrosta-4,6-diene-3-one-17-carboxylic acid (3) and the known (+)-2,21-dihydroxypregna-4,6-diene-3,20-dione or 2-hydroxy-6,7-didehydrocortexone (4) pregnane-type steroids were isolated from C. dubia. In addition, (-)-11,4'-di-O-acetylcryptanoside A (1a) has been synthesized from the acetylation of 1. The structures of these compounds were determined by analysis of their spectroscopic data, with their cytotoxic and NKA inhibitory activities being evaluated. In contrast to 1 that exhibited potent activities, the other compounds were largely inactive. Molecular docking profiles indicated that 1-3 and 1a bind to NKA, but some subtle differences were observed in their interactions with NKA, which may contribute to their differential cytotoxic and NKA inhibitory potency.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"183-190"},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981970","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

Total Synthesis and Anti-Inflammatory Activity of Tectoridin and Related Isoflavone Glucosides. 鸢尾草苷及相关异黄酮苷的总合成及抗炎活性研究。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-01-24 Epub Date: 2024-12-28 DOI: 10.1021/acs.jnatprod.4c01108

Hongbo Dong, Yuanwei You, Xiuli Yang, Ling Mei, Yufei Che, Na Wang, Ting Peng, Yujiao He

引用次数: 0

Breviane Spiroditerpenoids with Anti-inflammatory and Antiviral Activities from Deep-Sea-Derived Fungus Penicillium sp. F59. 深海来源真菌青霉菌sp. F59中具有抗炎和抗病毒活性的短针烷类蜘蛛萜。

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.4c00997

Yinghui Lv, Wenping Song, Zongze Shao, Tianlei Ying, Bihong Hong, Wenjing Tian, Siwen Niu

{"title":"Breviane Spiroditerpenoids with Anti-inflammatory and Antiviral Activities from Deep-Sea-Derived Fungus Penicillium sp. F59.","authors":"Yinghui Lv, Wenping Song, Zongze Shao, Tianlei Ying, Bihong Hong, Wenjing Tian, Siwen Niu","doi":"10.1021/acs.jnatprod.4c00997","DOIUrl":"10.1021/acs.jnatprod.4c00997","url":null,"abstract":"Twelve new breviane spiroditerpenoids, namely, chrysobreviones A-L (1-12), together with seven structurally related analogues (13-19) were isolated from the EtOAc extract of the fermented cultures of deep-sea-derived fungus Penicillium sp. F59. These structures including absolute configurations were resolved on the basis of extensive analysis of NMR spectroscopic data and HRESIMS, in association with experimental and calculated ECD data as well as the modified Mosher's method. Compound 1 represented the first breviane derivative containing an unusual octahydrodifuro[2,3-b:2',3'-d]furan moiety, while 7 and 9 were the first breviones featuring an epoxy ring and an 18-hydroxymethyl group, respectively. The anti-inflammatory and antiviral activities of compounds 1-19 were evaluated. Compounds 1, 8, 16, and 17 showed inhibitory effects against NO secretion in LPS-activated Raw264.7 macrophage cells with IC50 values ranging from 1.4 to 12.9 μM, while 1 and 7 exhibited antiviral effects against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) omicron subvariant BA.2 pseudovirus with IC50 values of 8.5 and 10.3 μM, respectively.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"67-79"},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833095","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