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Targeted Isolation of Antiviral Labdane Diterpenes from the Bark of Neo-uvaria foetida (Annonaceae) using LC-MS/MS-Based Molecular Networking.
IF 3.3 2区 生物学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-19 DOI: 10.1021/acs.jnatprod.4c00342
S Yaallini Sukumaran, Charline Herrscher, Nurulfazlina Edayah Rasol, Muhamad Aqmal Othman, Sook Yee Liew, Nor Hadiani Ismail, Karin Séron, Marc Litaudon, Khalijah Awang, Chaker El Kalamouni, Cécile Apel, Azeana Zahari

In the search of new inhibitors for human coronavirus (HCoV), we screened extracts of endemic Annonaceae plants on an assay using a cellular model of Huh-7 cells infected with the human alphacoronavirus HCoV-229E. The EtOAc bark extract of the rare Southeast Asian plant Neo-uvaria foetida exhibited inhibition of HCoV-229E and SARS-CoV-2 viruses with IC50 values of 3.8 and 7.8 μg/mL, respectively. Using LC-MS/MS and molecular networking analysis guided isolation, we discovered two new labdane-type diterpenoids, 8-epi-acuminolide (1) and foetidalabdane A (4), and three known labdane diterpenoids, acuminolide (2), 17-O-acetylacuminolide (3), and spiroacuminolide (5). A new norlabdane diterpene, 16-foetinorlabdoic acid (6), was also isolated and identified. Excluding compounds 5 and 6, all other metabolites were active against the virus HCoV-229E. Terpenoids 1 and 4 presented antiviral activity against SARS-CoV-2 with IC50 values of 63.3 and 93.5 μM, respectively, indicating lower potency. Additionally, virological assays demonstrated that compounds 1, 2, and 3 exert antiviral effects against Zika virus by specifically interfering with the late stage of its infectious cycle with IC50 values of 76.0, 31.9, and 14.9 μM, respectively.

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引用次数: 0
Wajeepeptin, a Cytotoxic and Antitrypanosomal Cyclic Depsipeptide from a Marine Moorena sp. Cyanobacterium. Wajeepeptin,一种来自海洋 Moorena sp.
IF 3.3 2区 生物学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-17 DOI: 10.1021/acs.jnatprod.4c00499
Naoaki Kurisawa, Ghulam Jeelani, Tomoyoshi Nozaki, Adnan Luthfi Agusta, Kiyotake Suenaga, Arihiro Iwasaki

Here, we report wajeepeptin (1), a new cyclic depsipeptide isolated from a marine Moorena sp. cyanobacterium. The structure was elucidated by a combination of spectroscopic analyses, X-ray diffraction analysis, and degradation reactions. Wajeepeptin (1) showed moderate cytotoxicity (IC50 = 3.7 μM against HeLa cells) and potent antitrypanosomal activity (IC50 = 0.73 ± 0.14 μM against Trypanosoma brucei rhodesiense).

在此,我们报告了从海洋 Moorena sp.蓝藻中分离出的一种新的环状去肽--wajeepeptin(1)。通过光谱分析、X 射线衍射分析和降解反应等综合方法阐明了其结构。Wajeepeptin (1) 对 HeLa 细胞表现出中等的细胞毒性(IC50 = 3.7 μM)和强效的抗锥虫活性(IC50 = 0.73 ± 0.14 μM)。
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引用次数: 0
Structure Determination of 1,3-Dioxolane-Containing Lipids from the Marine Sponge Leucetta sp. Using Chiral 1H NMR Analysis of Model Systems. 利用模型系统的手性 1H NMR 分析确定海洋海绵 Leucetta sp.
IF 3.3 2区 生物学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-17 DOI: 10.1021/acs.jnatprod.4c00692
A-Young Shin, Jihoon Lee

Chemical investigation of n-hexane extract from the marine sponge Leucetta sp. led to the isolation of five new lipids, 1-5, each characterized by a substituted dioxolane core. The structures of 1-5 were established based on the interpretation of NMR and HRESIMS data. To assign the absolute configuration at C-1', model systems consisting of diastereomers at C-2, C-4, and C-1' of the dioxolane core were prepared from a chiral glycerol dimethylacetal. 1H NMR inspection of model compounds revealed that a pair of C-1' epimers, 11a/c and 11b/d, was indistinguishable, restricting structural assignment by direct comparison of NMR data. In addition, the lack of chromophores in the dioxolane core resulted in unreliable ECD results, with Cotton effects appearing below 190 nm. As an alternative, a chiral NMR method using Eu(hfc)3 revealed notable lanthanide-induced shifts, allowing the spectroscopic discrimination of 11a/c and ent-11a/c. Therefore, the absolute configuration of all five new lipids was determined to be 2S, 4S, 1'S by direct comparison with the Eu(hfc)3-induced 1H NMR data.

通过对海洋海绵 Leucetta sp.的正己烷提取物进行化学研究,分离出了五种新的脂质(1-5),每种脂质的特征都是以取代的二氧戊环为核心。根据核磁共振和 HRESIMS 数据的解释,确定了 1-5 的结构。为了确定 C-1' 的绝对构型,利用手性甘油二甲基缩醛制备了由二氧戊环核心的 C-2、C-4 和 C-1' 非对映异构体组成的模型系统。对模型化合物进行的 1H NMR 检查发现,一对 C-1' 对映异构体(11a/c 和 11b/d)无法区分,这限制了通过直接比较 NMR 数据来确定结构。此外,由于二氧戊环核心缺乏发色团,导致 ECD 结果不可靠,在 190 纳米以下出现了棉花效应。作为替代方法,使用 Eu(hfc)3 的手性 NMR 方法显示了明显的镧系元素诱导的位移,从而可以在光谱上区分 11a/c 和 ent-11a/c。因此,通过与 Eu(hfc)3 诱导的 1H NMR 数据直接比较,确定了所有五种新脂类的绝对构型为 2S、4S、1'S。
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引用次数: 0
Highly Functionalized Spirobisnaphthalenes from Roussoella sp. KT4147. 来自 Roussoella sp. KT4147 的高功能化螺双萘。
IF 3.3 2区 生物学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-17 DOI: 10.1021/acs.jnatprod.4c00418
Taichiro Tokizaki, Ryuhi Kanehara, Hayato Maeda, Kazuaki Tanaka, Masaru Hashimoto

Highly functionalized spirobisnaphthalenes, preussomerins N (1) and O (2), and simpler compounds, such as 2,3-α-epoxypalmarumycin CP18 (3), 3α-hydroxy-CJ-12,372 (4), and 16 known structurally related congeners, were isolated from a culture broth of Roussoella sp. KT4147. Structural analysis revealed that 1 was a dimer of preussomerin G (6), connected by a nitrogen atom, and 2 was a derivative of 6 with a macommelin substructure. Preussomerin N (1) was considered to be biosynthetically derived via the Michael-type 1,4-addition of ammonia to 6, followed by another Michael addition to another molecule of 6. Contrarily, 2 was suggested to be derived through an endo-Diels-Alder cycloaddition between a diene derived from the (E)-enol form of macommelinal via an ene-reaction and dienophile 6. Compounds 1 and 2 exhibited potent cytotoxicity against COLO-201 human colorectal cancer cells.

从 Roussoella sp. KT4147 的培养液中分离出了高官能度螺双萘、preussomerins N (1) 和 O (2),以及更简单的化合物,如 2,3-α-epoxypalmarumycin CP18 (3)、3α-hydroxy-CJ-12,372 (4) 和 16 个已知结构相关的同系物。结构分析表明,1 是由一个氮原子连接的预苏木素 G(6)的二聚体,2 是具有大孔霉素亚结构的 6 的衍生物。Preussomerin N(1)被认为是通过将氨与 6 进行迈克尔式 1,4 加成,然后再与另一个 6 分子进行迈克尔加成而得到的生物合成物;相反,2 则被认为是通过大黄素 (E)-enol 形式的二烯通过烯-反应与亲二烯 6 进行内-Diels-Alder 环加成而得到的。化合物 1 和 2 对 COLO-201 人类结直肠癌细胞具有很强的细胞毒性。
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引用次数: 0
Dactylfungins and Tetralones: Bioactive Metabolites from a Nematode-Associated Laburnicola nematophila. Dactylfungins and Tetralones:来自线虫相关 Laburnicola nematophila 的生物活性代谢物。
IF 3.3 2区 生物学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-16 DOI: 10.1021/acs.jnatprod.4c00623
Jan-Peer Wennrich, Caren Holzenkamp, Miroslav Kolařík, Wolfgang Maier, Attila Mándi, Tibor Kurtán, Samad Ashrafi, Sherif S Ebada, Marc Stadler

A chemical investigation of Laburnicola nematophila, isolated from cysts of the plant parasitic nematode Heterodera filipjevi, affored three dactylfungin derivatives (1-3) and three tetralone congeners (4-6). Dactylfungin C (1), laburnicolin (4), and laburnicolenone (5) are previously undescribed natural products. Chemical structures of the isolated compounds were determined based on 1D and 2D NMR spectroscopic analyses together with HR-ESI-MS spectrometry and comparison with data reported in the literature. The relative configurations of compounds 1, 2, and 4-6 were determined based on their ROESY data and analysis of their coupling constants (J values). The absolute configurations of 4-6 were determined through the comparison of their measured and calculated TDDFT-ECD spectra. Compounds 1-3 were active against azole-resistant Aspergillus fumigatus.

对从植物寄生线虫 Heterodera filipjevi 的子囊中分离出来的 Laburnicola nematophila 进行了化学研究,发现了三种双触角菌素衍生物(1-3)和三种四氢萘酮同系物(4-6)。Dactylfungin C(1)、laburnicolin(4)和laburnicolenone(5)是以前未曾描述过的天然产物。根据一维和二维核磁共振光谱分析以及 HR-ESI-MS 光谱分析,并与文献报道的数据进行比较,确定了分离化合物的化学结构。化合物 1、2 和 4-6 的相对构型是根据其 ROESY 数据和耦合常数(J 值)分析确定的。4-6 的绝对构型是通过比较测量和计算的 TDDFT-ECD 光谱确定的。化合物 1-3 对抗唑曲霉具有活性。
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引用次数: 0
Chemoreactive 2,5-Diketopiperazines from a Penicillium sp., Structure Revision of Reported Analogues and Proposed Facile Transformation Pathways. 一种青霉菌的化学活性 2,5-二酮哌嗪、已报道类似物的结构修订以及拟议的简便转化途径。
IF 3.3 2区 生物学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-12 DOI: 10.1021/acs.jnatprod.4c00478
Quan T Khong, Emily A Smith, Karen L Wendt, Masoumeh Dalilian, Ekaterina I Goncharova, Isaac Brownell, Robert H Cichewicz, Curtis J Henrich, John A Beutler, Barry R O'Keefe, Lin Du

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous cancer. Two new prenylated indole 2,5-diketopiperazine alkaloids, brevianamides E1 (1) and E2 (2), were isolated from a Penicillium fungus. Both compounds showed moderate cytotoxic activity against select MCC cell lines (i.e., MCC13, MKL-1, UISO, and WaGa) in the low micromolar range. The relative and absolute configurations of 1 and 2 were determined by combined approaches, including NOESY spectroscopy, DFT ECD and DP4 plus calculations, and Marfey's reaction. Literature research and the comparison of NMR and ECD data led to the structure revision of three previously reported natural analogues, notoamides K and P and asperversiamide L. The structurally unstable 1 and 2 underwent steady interconversion under neutral aqueous conditions. Investigation of the degradation of 2 in acidic methanol solutions led to the identification of a new methoxylated derivative (6) and two new ring-opened products (7 and 8) with the rearranged, elongated, 4-methylpent-3-ene side chain. The facile transformation of 2 to 7 and 8 was promoted by the intrinsic impurity (i.e., formaldehyde) of HPLC-grade methanol through the aza-Cope rearrangement.

梅克尔细胞癌(MCC)是一种罕见的侵袭性皮肤癌。从一种青霉真菌中分离出了两种新的前酰化吲哚-2,5-二酮哌嗪生物碱,即brevianamides E1 (1)和E2 (2)。这两种化合物对选定的 MCC 细胞系(即 MCC13、MKL-1、UISO 和 WaGa)均显示出中等程度的细胞毒性活性,且活性范围在低微摩尔范围内。1 和 2 的相对和绝对构型是通过综合方法确定的,包括 NOESY 光谱、DFT ECD 和 DP4 plus 计算以及 Marfey 反应。通过文献研究以及核磁共振和 ECD 数据的比较,对之前报道的三种天然类似物(艽酰胺 K 和 P 以及阿斯佩尔韦斯酰胺 L)的结构进行了修正。通过研究 2 在酸性甲醇溶液中的降解过程,发现了一种新的甲氧基化衍生物(6)和两种新的开环产物(7 和 8),这两种产物的侧链是重新排列的、拉长的 4-甲基戊-3-烯。高效液相色谱级甲醇中的固有杂质(即甲醛)通过偶氮-科普重排促进了 2 向 7 和 8 的简单转化。
{"title":"Chemoreactive 2,5-Diketopiperazines from a <i>Penicillium</i> sp., Structure Revision of Reported Analogues and Proposed Facile Transformation Pathways.","authors":"Quan T Khong, Emily A Smith, Karen L Wendt, Masoumeh Dalilian, Ekaterina I Goncharova, Isaac Brownell, Robert H Cichewicz, Curtis J Henrich, John A Beutler, Barry R O'Keefe, Lin Du","doi":"10.1021/acs.jnatprod.4c00478","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00478","url":null,"abstract":"<p><p>Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous cancer. Two new prenylated indole 2,5-diketopiperazine alkaloids, brevianamides E1 (<b>1</b>) and E2 (<b>2</b>), were isolated from a <i>Penicillium</i> fungus. Both compounds showed moderate cytotoxic activity against select MCC cell lines (i.e., MCC13, MKL-1, UISO, and WaGa) in the low micromolar range. The relative and absolute configurations of <b>1</b> and <b>2</b> were determined by combined approaches, including NOESY spectroscopy, DFT ECD and DP4 plus calculations, and Marfey's reaction. Literature research and the comparison of NMR and ECD data led to the structure revision of three previously reported natural analogues, notoamides K and P and asperversiamide L. The structurally unstable <b>1</b> and <b>2</b> underwent steady interconversion under neutral aqueous conditions. Investigation of the degradation of <b>2</b> in acidic methanol solutions led to the identification of a new methoxylated derivative (<b>6</b>) and two new ring-opened products (<b>7</b> and <b>8</b>) with the rearranged, elongated, 4-methylpent-3-ene side chain. The facile transformation of <b>2</b> to <b>7</b> and <b>8</b> was promoted by the intrinsic impurity (i.e., formaldehyde) of HPLC-grade methanol through the aza-Cope rearrangement.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588932","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
Discovery of Uncommon Tryptophan-Containing Diketopiperazines from Aspergillus homomorphus CBS 101889 Using an Aspergillus nidulans Heterologous Expression System. 利用黑曲霉异源表达系统从同型曲霉 CBS 101889 中发现不常见的含色氨酸的二酮哌嗪。
IF 3.3 2区 生物学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-11 DOI: 10.1021/acs.jnatprod.4c00113
Cory B Jenkinson, Shu-Yi Lin, Mary Villarreal, C Elizabeth Oakley, David H Sherman, Ching-Kuo Lee, Clay C C Wang, Berl R Oakley

Fungal secondary metabolite (SM) biosynthetic gene clusters (BGCs) containing dimethylallyltryptophan synthases (DMATSs) produce structurally diverse prenylated indole alkaloids with wide-ranging activities that have vast potential as human therapeutics. To discover new natural products produced by DMATSs, we mined the Department of Energy Joint Genome Institute's MycoCosm database for DMATS-containing BGCs. We found a DMATS BGC in Aspergillus homomorphus CBS 101889, which also contains a nonribosomal peptide synthetase (NRPS). This BGC appeared to have a previously unreported combination of genes, which suggested the cluster might make novel SMs. We refactored this BGC with highly inducible promoters into the model fungus Aspergillus nidulans. The expression of this refactored BGC in A. nidulans resulted in the production of eight tryptophan-containing diketopiperazines, six of which are new to science. We have named them homomorphins A-F (2, 4-8). Perhaps even more intriguingly, to our knowledge, this is the first discovery of C4-prenylated tryptophan-containing diketopiperazines and their derivatives. In addition, the NRPS from this BGC is the first described that has the ability to promiscuously combine tryptophan with either of two different amino acids, in this case, l-valine or l-allo-isoleucine.

含有二甲基烯丙基色氨酸合成酶(DMATSs)的真菌次生代谢物(SM)生物合成基因簇(BGCs)产生结构多样的前酰化吲哚生物碱,这些生物碱具有广泛的活性,作为人类治疗药物具有巨大的潜力。为了发现由DMATS产生的新天然产物,我们在能源部联合基因组研究所的MycoCosm数据库中挖掘了含有DMATS的BGCs。我们在同形曲霉 CBS 101889 中发现了一种 DMATS BGC,它还含有一种非核糖体肽合成酶(NRPS)。该BGC似乎具有以前未报道过的基因组合,这表明该基因簇可能制造新型SMs。我们用高度可诱导的启动子将这一BGC重构到模式真菌黑曲霉中。在裸曲曲霉中表达重构的 BGC 后,产生了八种含色氨酸的二酮哌嗪,其中六种是科学界新发现的。我们将它们命名为同构态蛋白 A-F(2,4-8)。也许更令人感兴趣的是,据我们所知,这是首次发现 C4-异戊烯化的含色氨酸二酮哌嗪及其衍生物。此外,该 BGC 的 NRPS 是第一个能够将色氨酸与两种不同氨基酸(在本例中为 l-缬氨酸或 l-异亮氨酸)中的任何一种杂交结合的 NRPS。
{"title":"Discovery of Uncommon Tryptophan-Containing Diketopiperazines from <i>Aspergillus homomorphus</i> CBS 101889 Using an <i>Aspergillus nidulans</i> Heterologous Expression System.","authors":"Cory B Jenkinson, Shu-Yi Lin, Mary Villarreal, C Elizabeth Oakley, David H Sherman, Ching-Kuo Lee, Clay C C Wang, Berl R Oakley","doi":"10.1021/acs.jnatprod.4c00113","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00113","url":null,"abstract":"<p><p>Fungal secondary metabolite (SM) biosynthetic gene clusters (BGCs) containing dimethylallyltryptophan synthases (DMATSs) produce structurally diverse prenylated indole alkaloids with wide-ranging activities that have vast potential as human therapeutics. To discover new natural products produced by DMATSs, we mined the Department of Energy Joint Genome Institute's MycoCosm database for DMATS-containing BGCs. We found a DMATS BGC in <i>Aspergillus homomorphus</i> CBS 101889, which also contains a nonribosomal peptide synthetase (NRPS). This BGC appeared to have a previously unreported combination of genes, which suggested the cluster might make novel SMs. We refactored this BGC with highly inducible promoters into the model fungus <i>Aspergillus nidulans</i>. The expression of this refactored BGC in <i>A</i>. <i>nidulans</i> resulted in the production of eight tryptophan-containing diketopiperazines, six of which are new to science. We have named them homomorphins A-F (<b>2</b>, <b>4</b>-<b>8</b>). Perhaps even more intriguingly, to our knowledge, this is the first discovery of C4-prenylated tryptophan-containing diketopiperazines and their derivatives. In addition, the NRPS from this BGC is the first described that has the ability to promiscuously combine tryptophan with either of two different amino acids, in this case, l-valine or l-<i>allo</i>-isoleucine.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578157","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
NMR-Guided Isolation of Anti-inflammatory Carabranolides from the Fruits of Carpesium abrotanoides L. 核磁共振引导从胭脂虫果实中分离出抗炎性胡罗卜素内酯
IF 3.3 2区 生物学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-10 DOI: 10.1021/acs.jnatprod.4c00338
Lu Fu, Can-Can Wang, Wenyue Tian, Zhiyan Liu, Meng-Yu Bao, Jiazheng Liu, Wei Zhang, Li-Ping Bai, Zhi-Hong Jiang, Guo-Yuan Zhu

Carabranolides present characteristic NMR resonances for the cyclopropane moiety, which distinctly differ from those of other compounds and were used for an NMR-guided isolation in this study. As a result, 11 undescribed carabranolides (1-11), along with five known ones (12-16), were isolated from the fruits of Carpesium abrotanoides L. Compounds 1-11 are new esters of carabrol at C-4 with different carboxylic acids. Their structures were elucidated by HRESIMS and NMR spectroscopic data analysis. The biological evaluation showed that compounds 2-4, 15, and 16 exhibited significant inhibitory activity against LPS-induced NO release with an IC50 value of 5.6-9.1 μM and dose-dependently decreased iNOS protein expression in RAW264.7 cells.

胡蔓藤内酯的环丙烷分子具有特征性核磁共振共振,与其他化合物的共振明显不同,本研究利用这些共振进行核磁共振引导分离。结果,从胡颓子果实中分离出了 11 种未描述的胡颓子内酯(1-11)和 5 种已知的胡颓子内酯(12-16)。通过 HRESIMS 和 NMR 光谱数据分析阐明了它们的结构。生物学评价表明,化合物 2-4、15 和 16 对 LPS 诱导的 NO 释放具有显著的抑制活性,IC50 值为 5.6-9.1 μM,并能剂量依赖性地降低 RAW264.7 细胞中 iNOS 蛋白的表达。
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引用次数: 0
Characterization of Sesquiterpene Dimers from the Flowers of Inula japonica and the Structural Revisions of Related Compounds. 茵陈花中半萜二聚体的表征及相关化合物的结构修正
IF 3.3 2区 生物学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-09 DOI: 10.1021/acs.jnatprod.4c00269
Zheng Niu, Chun-Yan Chen, Yan Zhou, Guan-Ke Liu, Bing-Yang Zhang, Mahmood Brobbey Oppong, De-Qin Zhang, Tie Yao, Feng Qiu

Sesquiterpene dimers are mainly found in the Asteraceae family. However, conflicting reports on the structures of these compounds can be found in the literature. Herein, we describe ten sesquiterpene dimers isolated from the flowers of Inula japonica, including configurational revisions of japonicone H (1-1), japonicone D (2-1), inulanolide A (4-1), japonicone X (5-1), and inulanolide F (5-2) to compounds 1, 2, 4, and 5, respectively. Five new related metabolites (3 and 6-9) are also described. Application of GIAO NMR/DP4+ analyses and ECD/OR calculations enabled us to revise the absolute configurations of an additional 13 sesquiterpene dimers isolated from plants of the genus Inula. Compounds 1, 2, 4, and 6 exhibited inhibition of nitric oxide production in lipopolysaccharide activated RAW264.7 macrophages with IC50 values of 4.07-10.00 μM.

倍半萜二聚体主要存在于菊科植物中。然而,文献中关于这些化合物结构的报道相互矛盾。在本文中,我们描述了从茵陈花中分离出的十种倍半萜二聚体,包括将日本忍冬内酯 H(1-1)、日本忍冬内酯 D(2-1)、菊内酯 A(4-1)、日本忍冬内酯 X(5-1)和菊内酯 F(5-2)分别与化合物 1、2、4 和 5 进行构型修正。此外,还介绍了五种新的相关代谢物(3 和 6-9)。应用 GIAO NMR/DP4+ 分析和 ECD/OR 计算,我们修正了从茵陈属植物中分离出的另外 13 个倍半萜二聚体的绝对构型。化合物 1、2、4 和 6 能抑制脂多糖激活的 RAW264.7 巨噬细胞产生一氧化氮,IC50 值为 4.07-10.00 μM。
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引用次数: 0
Genome-Driven Discovery of Antiviral Atralabdans A-C from the Soil-Dwelling Streptomyces atratus. 基因组驱动从土栖链霉菌中发现抗病毒的 Atralabdans A-C。
IF 3.3 2区 生物学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-08 DOI: 10.1021/acs.jnatprod.4c00225
Ling Shen, Yanyan Wang, Chengxin Liu, Wula Alateng, Yuxin Wang, Axel Zeeck, Weiguang Wang, Peng Zhang, Yanhong Wei, Xiaofeng Cai

Heterologous expression of an atr terpenoid gene cluster derived from Streptomyces atratus Gö66 in S. albus J1074 led to the discovery of three novel labdane diterpenoids featuring an unprecedented 6/6/5-fused tricyclic skeleton, designated as atralabdans A-C (1-3), along with a known compound, labdanmycin A. Compounds 1-3 were identified through extensive spectroscopic analysis, including NMR calculations with DP4+ probability analysis, and a comparative assessment of experimental and theoretical electronic circular dichroism (ECD) spectra. A plausible biosynthetic pathway for these compounds was proposed. Compounds 1-3 exhibited inhibitory activity against the human neurotropic coxsackievirus B3 (CVB3); 1 was the most potent, surpassing the positive control ribavirin with a higher therapeutic index.

通过在 S. albus J1074 中异源表达源自阿特拉普氏链霉菌 Gö66 的阿特拉普氏萜类化合物基因簇,发现了三种新型拉班二萜,它们具有前所未有的 6/6/5 融合三环骨架,与已知化合物拉班霉素 A 一起被命名为阿特拉普氏萜 A-C(1-3)。通过广泛的光谱分析,包括利用 DP4+ 概率分析进行核磁共振计算,以及对实验和理论电子圆二色性(ECD)光谱进行比较评估,确定了 1-3 号化合物。提出了这些化合物的合理生物合成途径。化合物 1-3 对人类神经性柯萨奇病毒 B3(CVB3)具有抑制活性;其中化合物 1 的效力最强,以更高的治疗指数超过了阳性对照利巴韦林。
{"title":"Genome-Driven Discovery of Antiviral Atralabdans A-C from the Soil-Dwelling <i>Streptomyces atratus</i>.","authors":"Ling Shen, Yanyan Wang, Chengxin Liu, Wula Alateng, Yuxin Wang, Axel Zeeck, Weiguang Wang, Peng Zhang, Yanhong Wei, Xiaofeng Cai","doi":"10.1021/acs.jnatprod.4c00225","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00225","url":null,"abstract":"<p><p>Heterologous expression of an <i>atr</i> terpenoid gene cluster derived from <i>Streptomyces atratus</i> Gö66 in <i>S. albus</i> J1074 led to the discovery of three novel labdane diterpenoids featuring an unprecedented 6/6/5-fused tricyclic skeleton, designated as atralabdans A-C (<b>1</b>-<b>3</b>), along with a known compound, labdanmycin A. Compounds <b>1</b>-<b>3</b> were identified through extensive spectroscopic analysis, including NMR calculations with DP4+ probability analysis, and a comparative assessment of experimental and theoretical electronic circular dichroism (ECD) spectra. A plausible biosynthetic pathway for these compounds was proposed. Compounds <b>1</b>-<b>3</b> exhibited inhibitory activity against the human neurotropic coxsackievirus B3 (CVB3); <b>1</b> was the most potent, surpassing the positive control ribavirin with a higher therapeutic index.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557403","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
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