37 results on '"Xiachang Wang"'
Search Results
2. Dendrocrepidamine, a novel octahydroindolizine alkaloid from the roots of Dendrobium crepidatum
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Xiaoqian Ding, Yu-Qing Zou, Yang Hu, Xiachang Wang, Chaofeng Zhang, Xiao Liu, and Jian Liu
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Pharmacology ,Ethanol ,Lipopolysaccharide ,biology ,010405 organic chemistry ,Stereochemistry ,Alkaloid ,Organic Chemistry ,Pharmaceutical Science ,General Medicine ,Lung injury ,Dendrobium crepidatum ,biology.organism_classification ,01 natural sciences ,0104 chemical sciences ,Analytical Chemistry ,Nitric oxide ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,Complementary and alternative medicine ,chemistry ,In vivo ,Drug Discovery ,Molecular Medicine ,Bibenzyl - Abstract
A novel octahydroindolizine alkaloid, named dendrocrepidamine (1) with an unusual 18,19,19'-cyclopropanone-dendrocrepine skeleton, was isolated from the ethanol extract of the roots of Dendrobium crepidatum, along with six known compounds (2-7). The structure of 1 was elucidated through HR-ESIMS, NMR spectroscopic data and computational calculations. All compounds were examined for their inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 cells with IC50 values in the range of 3.04-54.89 µM. In vivo, crepidatin (6) (80, 40 and 10 mg/kg) showed a significant protective effect against LPS-induced acute lung injury (ALI) in mice.
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- 2021
3. The crystal structure of <scp>AbsH3</scp> : A putative flavin adenine dinucleotide‐dependent reductase in the abyssomicin biosynthesis pathway
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Jon S. Thorson, Wenlong Cai, George N. Phillips, Yanyan Zhu, Steven G. Van Lanen, Jonathan A. Clinger, Mitchell D. Miller, Chang-Guo Zhan, and Xiachang Wang
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Flavin adenine dinucleotide ,chemistry.chemical_classification ,0303 health sciences ,Natural product ,biology ,030302 biochemistry & molecular biology ,Flavin group ,Reductase ,biology.organism_classification ,Biochemistry ,Streptomyces ,03 medical and health sciences ,chemistry.chemical_compound ,Biosynthesis ,chemistry ,Structural Biology ,Oxidoreductase ,Gene cluster ,Molecular Biology ,030304 developmental biology - Abstract
Natural products and natural product-derived compounds have been widely used for pharmaceuticals for many years, and the search for new natural products that may have interesting activity is ongoing. Abyssomicins are natural product molecules that have antibiotic activity via inhibition of the folate synthesis pathway in microbiota. These compounds also appear to undergo a required [4 + 2] cycloaddition in their biosynthetic pathway. Here we report the structure of an flavin adenine dinucleotide-dependent reductase, AbsH3, from the biosynthetic gene cluster of novel abyssomicins found in Streptomyces sp. LC-6-2.
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- 2020
4. Chartspiroton, a Tetracyclic Spiro-naphthoquinone Derivative from a Medicinal Plant Endophytic Streptomyces
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Tian Xie, Xiachang Wang, Sheng Bao, Huimin Zhao, Tianjie Yuan, Yang Hu, Jian Liu, Qichun Zhang, Shurong Hou, Aiping Yang, Xiabin Chen, Peng Ren, and Lihong Hu
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chemistry.chemical_classification ,biology ,010405 organic chemistry ,Stereochemistry ,Organic Chemistry ,010402 general chemistry ,biology.organism_classification ,Ring (chemistry) ,01 natural sciences ,Biochemistry ,Streptomyces ,Naphthoquinone ,0104 chemical sciences ,chemistry.chemical_compound ,Polyketide ,chemistry ,Moiety ,Physical and Theoretical Chemistry ,Benzofuran ,Derivative (chemistry) ,Lactone - Abstract
A novel 6/6/5/6 tetracyclic polyketide named chartspiroton (1) was isolated from a medicinal plant endophytic Streptomyces in Dendrobium officinale. The complete structure assignment with absolute stereochemistry was elucidated through spectroscopic data, computational calculations, and single-crystal X-ray diffraction. Chartspiroton features an unprecedented naphthoquinone derivative spiro-fused with a benzofuran lactone moiety. A plausible polyketide biosynthetic pathway for 1 suggested intriguing oxidative rearrangement steps to form the five-membered lactone ring.
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- 2020
5. Insecticidal Endostemonines A–J Produced by Endophytic Streptomyces from Stemona sessilifolia
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Chang Wang, Xiachang Wang, Li Shiyang, Lihong Hu, Huimin Zhao, Sheng Bao, Aiping Yang, Yinan Zhang, Nan Zhang, Tianjie Yuan, Ning Ding, and Siwang Zhang
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0106 biological sciences ,Traditional medicine ,business.industry ,010401 analytical chemistry ,Pest control ,Stemona sessilifolia ,General Chemistry ,Biology ,Secondary metabolite ,Pesticide ,biology.organism_classification ,01 natural sciences ,Streptomyces ,Endophyte ,0104 chemical sciences ,Crop protection ,Aphis gossypii ,medicine ,General Agricultural and Biological Sciences ,business ,010606 plant biology & botany ,medicine.drug - Abstract
The discovery of new, safe, and effective pesticides is one of the main means for modern crop protection and parasitic disease control. During the search for new insecticidal secondary metabolites from endophytes in Stemona sessilifolia (a traditional Chinese medicine with a long history as an insecticide), 10 new insecticidal endostemonines A-J (1-10) were identified from an endophytic Streptomyces sp. BS-1. Their structures were determined by comprehensive spectroscopic analysis. Endostemonines A-J represent the first reported naturally occurring pyrrole-2-carboxylic ester derivatives, which consisted of different fatty acid chains at the C-2 of pyrrole ring were produced by traditional Chinese medicine endophytic microbes. All new tested compounds exhibited strong lethal activity against Aphis gossypii (LC50 value range of 3.55-32.00 mg/L after 72 h). This research highlighted the discovery of pesticide natural products from insecticidal medicinal plant endophytes for the first time, paving a new pathway for the development of pest control.
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- 2020
6. Structure Determination, Functional Characterization, and Biosynthetic Implications of Nybomycin Metabolites from a Mining Reclamation Site-Associated Streptomyces
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Bruce E. Hatcher, Gregory C. Copley, Jon S. Thorson, Xiachang Wang, James C. Hower, Yang Liu, Madan K. Kharel, Qing-Bai She, Steven G. Van Lanen, Larissa V. Ponomareva, Khaled A. Shaaban, Sherif I. Elshahawi, S. Randal Voss, and Qing Ye
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Antifungal Agents ,Pharmaceutical Science ,Quinolones ,Gram-Positive Bacteria ,01 natural sciences ,Streptomyces ,Article ,Analytical Chemistry ,Cell Line, Tumor ,Drug Discovery ,Humans ,Deoxynyboquinone ,Cytotoxicity ,Pharmacology ,Molecular Structure ,biology ,Strain (chemistry) ,010405 organic chemistry ,Chemistry ,Spectrum Analysis ,Regeneration (biology) ,Organic Chemistry ,Translation (biology) ,biology.organism_classification ,Anti-Bacterial Agents ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Complementary and alternative medicine ,Biochemistry ,Cell culture ,Molecular Medicine ,Phosphorylation ,Drug Screening Assays, Antitumor - Abstract
We report the isolation and characterization of three new nybomycins (nybomycins B–D, 1–3) and six known compounds (nybomycin, 4; deoxynyboquinone, 5; α-rubromycin, 6; β-rubromycin, 7; γ-rubromycin, 8; and [2α(1E,3E),4β]-2-(1,3-pentadienyl)-4-piperidinol, 9) from the Rock Creek (McCreary County, KY) underground coal mine acid reclamation site isolate Streptomyces sp. AD-3-6. Nybomycin D (3) and deoxynyboquinone (5) displayed moderate (3) to potent (5) cancer cell line cytotoxicity and displayed weak to moderate anti-Gram-(+) bacterial activity, whereas rubromycins 6–8 displayed little to no cancer cell line cytotoxicity but moderate to potent anti-Gram-(+) bacterial and antifungal activity. Assessment of the impact of 3 or 5 cancer cell line treatment on 4E-BP1 phosphorylation, a predictive marker of ROS-mediated control of cap-dependent translation, also revealed deoxynyboquinone (5)-mediated downstream inhibition of 4E-BP1p. Evaluation of 1–9 in a recently established axolotl embryo tail regeneration assay also highlighted the prototypical telomerase inhibitor γ-rubromycin (8) as a new inhibitor of tail regeneration. Cumulatively, this work highlights an alternative nybomycin production strain, a small set of new nybomycin metabolites, and previously unknown functions of rubromycins (antifungal activity and inhibition of tail regeneration) and also provides a basis for revision of the previously proposed nybomycin biosynthetic pathway.
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- 2019
7. Baraphenazines A–G, Divergent Fused Phenazine-Based Metabolites from a Himalayan Streptomyces
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Sherif I. Elshahawi, Khaled A. Shaaban, Larissa V. Ponomareva, Jon S. Thorson, Xiachang Wang, Steven G. Van Lanen, Muhammad Abbas, S. Randal Voss, Imran Sajid, Yinan Zhang, and Zheng Cui
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Stereochemistry ,Metabolite ,Phenazine ,Pharmaceutical Science ,01 natural sciences ,Streptomyces ,Article ,Analytical Chemistry ,chemistry.chemical_compound ,Quinoxalines ,Drug Discovery ,Pharmacology ,chemistry.chemical_classification ,Molecular Structure ,biology ,010405 organic chemistry ,Extramural ,Organic Chemistry ,biology.organism_classification ,Bacterial strain ,Anti-Bacterial Agents ,0104 chemical sciences ,Amino acid ,010404 medicinal & biomolecular chemistry ,Complementary and alternative medicine ,chemistry ,Phenazines ,Molecular Medicine - Abstract
The structures and bioactivities of three unprecedented fused 5-hydroxyquinoxaline/alpha-keto acid amino acid metabolites (baraphenazines A–C, 1–3), two unique diastaphenazine-type metabolites (baraphenazines D and E, 4 and 5) and two new phenazinolin-type (baraphenazines F and G, 6 and 7) metabolites from the Himalayan isolate Streptomyces sp. PU-10A are reported. This study highlights the first reported bacterial strain capable of producing diastaphenazine-type, phenazinolin-type, and izumiphenazine A-type metabolites and presents a unique opportunity for the future biosynthetic interrogation of late-stage phenazine-based metabolite maturation.
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- 2019
8. Terragines F–G produced by endophytic Bacillus sp. SH-1.2-ROOT-18 from Dendrobium officinale
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Xiachang Wang, Jingyi Meng, Huimin Zhao, Li Shiyang, Yichao Kong, Xiabin Chen, Youjuan Zhu, Yuanzhuo Hu, and Shurong Hou
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Natural product ,biology ,010405 organic chemistry ,Stereochemistry ,Metabolite ,Organic Chemistry ,Plant Science ,Bacillus sp ,biology.organism_classification ,01 natural sciences ,Biochemistry ,Endophyte ,0104 chemical sciences ,Analytical Chemistry ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,Dendrobium officinale ,chemistry ,Succinimide ,Base (exponentiation) ,Two-dimensional nuclear magnetic resonance spectroscopy - Abstract
Two new terragine analogs (1‒2) with special succinimide and aminopentane moieties were isolated from the fermentation broth of Bacillus sp. SH-1.2-ROOT-18, an endophyte previously discovered from the root of Dendrobium officinale. The structures were elucidated base on comprehensive 1 D/2D NMR and MS data analysis. Complete NMR assignments for the first reported naturally occurring metabolite 3 was also provided.
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- 2021
- Full Text
- View/download PDF
9. The Anti-colitis Effect of Schisandra chinensis Polysaccharide Is Associated With the Regulation of the Composition and Metabolism of Gut Microbiota
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Lianlin Su, Chunqin Mao, Xiachang Wang, Lin Li, Huangjin Tong, Jing Mao, De Ji, Tulin Lu, Min Hao, Ziyan Huang, Chenghao Fei, Kewei Zhang, and Guojun Yan
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0301 basic medicine ,Microbiology (medical) ,Schisandra chinensis ,030106 microbiology ,Immunology ,lcsh:QR1-502 ,short chain fatty acid ,Inflammation ,Gut flora ,Microbiology ,Inflammatory bowel disease ,digestive system ,lcsh:Microbiology ,Pathogenesis ,Butyric acid ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Cellular and Infection Microbiology ,Polysaccharides ,medicine ,Animals ,Humans ,Colitis ,Original Research ,ulcerative colitis ,Schisandra ,biology ,gut microbiota ,Short-chain fatty acid ,Dextran Sulfate ,biology.organism_classification ,medicine.disease ,Ulcerative colitis ,Gastrointestinal Microbiome ,Disease Models, Animal ,030104 developmental biology ,Infectious Diseases ,chemistry ,inflammation ,polysaccharide ,Colitis, Ulcerative ,medicine.symptom - Abstract
Background: The pathogenesis of inflammatory bowel disease (IBD) is linked to an intricate association of environmental, microbial, and host-related factors. Polysaccharide affects host immunity by regulating the composition and metabolism of gut microbiota is the common mechanism of disease resistance. However, the efficacy and mechanism of Schisandra chinensis polysaccharide (SCP) in the treatment of inflammatory bowel disease have not been studied. Objective: To explore the effect and mechanism of SCP on dextran sodium sulfate (DSS) - induced ulcerative colitis (UC) in mice. Materials/Methods: In this study, we established a mouse model of UC, and used SCP for treatment intervention. The biochemical indexes related to inflammation were determined by ELISA kit, and the therapeutic effect of SCP on UC was clarified. Then, 16S rDNA sequencing was used to study the effect of SCP on the composition and diversity of gut microbiota. At the same time, GC-MS was used to determine the content of short chain fatty acids in intestinal contents. Finally, the relationship among gut microbiota, short chain fatty acids and inflammatory factors was analyzed, and to comprehensively explain the effect and mechanism of SCP on UC. Results: The results showed that SCP could significantly improve the physiological state of UC mice and regulate the level of inflammatory factors to normal levels. Meanwhile, SCP could significantly regulate the imbalance of gut microbiota and increase the content of SCFAs. In addition, the results of the correlation between gut microbiota and SCFAs showed that butyric acid, isobutyric acid and valeric acid had the highest correlation with gut microbiota. Conclusion: In conclusion, this research showed that SCP can inhibit inflammatory bowel disease by regulating the composition and metabolism of gut microbiota, and indicating that SCP may be used as adjuvant therapy for IBD patients.
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- 2020
10. The triterpenoid sapogenin (2α-OH-Protopanoxadiol) ameliorates metabolic syndrome via the intestinal FXR/GLP-1 axis through gut microbiota remodelling
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Sheng Bao, Xinwen Zhang, Xiachang Wang, Chen-dong Zhou, Wei Liu, Shui-mei Sun, Jing-Ya Li, Jia Li, Haowen Jiang, Lihong Hu, Jia Liu, Yinan Zhang, Dakai Chen, and Zhifu Xie
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Male ,Taurocholic Acid ,Cancer Research ,Metabolite ,Immunology ,Drug development ,Pharmacology ,Gut flora ,Diet, High-Fat ,Article ,Mice ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Glucagon-Like Peptide 1 ,RNA, Ribosomal, 16S ,medicine ,Animals ,Secretion ,lcsh:QH573-671 ,Metabolic Syndrome ,chemistry.chemical_classification ,Mice, Inbred ICR ,biology ,lcsh:Cytology ,Plant Extracts ,Diabetes ,RNA-Binding Proteins ,Cell Biology ,Glucagon ,medicine.disease ,biology.organism_classification ,Gastrointestinal Microbiome ,Gynostemma ,Intestines ,Mice, Inbred C57BL ,Transplantation ,Enzyme ,chemistry ,Nuclear receptor ,Drug Design ,Farnesoid X receptor ,Metabolic syndrome - Abstract
Gypenosides, extracts of Gynostemma yixingense, have been traditionally prescribed to improve metabolic syndrome in Asian folk and local traditional medicine hospitals. However, the mechanism of its action remains unclarified. In this work, our results indicated that chronic administration of 2α-OH-protopanoxadiol (GP2), a metabolite of gypenosides in vivo, protected mice from high-fat diet-induced obesity and improved glucose tolerance by improving intestinal L-cell function. Mechanistically, GP2 treatment inhibited the enzymatic activity of bile salt hydrolase and modulated the proportions of the gut microbiota, which led to an increase in the accumulation of tauro-β-muricholic acid (TβMCA) in the intestine. TβMCA induced GLP-1 production and secretion by reducing the transcriptional activity of nuclear receptor farnesoid X receptor (FXR). Transplantation of GP2-remodelled fecal microbiota into antibiotic-treated mice also increased the intestinal TβMCA content and improved intestinal L-cell function. These findings demonstrate that GP2 ameliorates metabolic syndrome at least partly through the intestinal FXR/GLP-1 axis via gut microbiota remodelling and also suggest that GP2 may serve as a promising oral therapeutic agent for metabolic syndrome.
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- 2020
11. The Crystal Structure of AbsH3: a Putative FAD-dependent Reductase in the Abyssomicin Biosynthesis Pathway
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George N. Phillips, Wenlong Cai, Chang-Guo Zhan, Xiachang Wang, Yanyan Zhu, Jonathan A. Clinger, Mitchell D. Miller, Jon S. Thorson, and Steven G. Van Lanen
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Biological Products ,Natural product ,biology ,Stereochemistry ,Crystal structure ,Reductase ,biology.organism_classification ,Streptomyces ,Cycloaddition ,Article ,Biosynthetic Pathways ,chemistry.chemical_compound ,chemistry ,Biosynthesis ,Gene cluster ,Flavin-Adenine Dinucleotide ,Oxidoreductases - Abstract
Natural products and natural product-derived compounds have been widely used for pharmaceuticals for many years, and the search for new natural products that may have interesting activity is ongoing. Abyssomicins are natural product molecules that have antibiotic activity via inhibition of the folate synthesis pathway in microbiota. These compounds also appear to undergo a required [4 + 2] cycloaddition in their biosynthetic pathway. Here we report the structure of an flavin adenine dinucleotide-dependent reductase, AbsH3, from the biosynthetic gene cluster of novel abyssomicins found in Streptomyces sp. LC-6-2.
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- 2020
12. Antibacterial Muraymycins from Mutant Strains of Streptomyces sp. NRRL 30471
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Xiachang Wang, Stefan Koppermann, Steven G. Van Lanen, Christian Ducho, Zheng Cui, and Jon S. Thorson
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Staphylococcus aureus ,Stereochemistry ,Mutant ,Pharmaceutical Science ,Mutagenesis (molecular biology technique) ,Microbial Sensitivity Tests ,010402 general chemistry ,medicine.disease_cause ,01 natural sciences ,Streptomyces ,Article ,Analytical Chemistry ,Drug Discovery ,Escherichia coli ,medicine ,Pharmacology ,chemistry.chemical_classification ,Aquifex aeolicus ,biology ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Fatty acid ,Nucleosides ,biology.organism_classification ,Anti-Bacterial Agents ,0104 chemical sciences ,Complementary and alternative medicine ,Molecular Medicine ,Antibacterial activity - Abstract
Muraymycins are nucleoside antibiotics isolated from Streptomyces sp. NRRL 30471 and several mutant strains thereof that were generated by random, chemical mutagenesis. Reinvestigation of two mutant strains using new media conditions led to the isolation of three new muraymycin congeners, named B8, B9, and C6 (1-3), as well as a known muraymycin, C1. Structures of the compounds were elucidated by HRMS and 1D and 2D NMR spectroscopic analyses. Complete 2D NMR assignments for the known muraymycin C1 are also provided for the first time. Compounds 1 and 2, which differ from other muraymycins by having an elongated, terminally branched fatty acid side chain, had picomolar IC50 values against Staphylococcus aureus and Aquifex aeolicus MraY and showed good antibacterial activity against S. aureus (MIC = 2 and 6 μg/mL, respectively) and Escherichia coli Δ tolC (MIC = 4 and 2 μg/mL, respectively). Compound 3, which is characterized by an N-acetyl modification of the primary amine of the dissacharide core that is shared among nearly all of the reported muraymycin congeners, greatly reduced its inhibitory and antibacterial activity compared to nonacylated muraymycin C1, which possibly indicates this modification is used for self-resistance.
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- 2018
13. Mccrearamycins A-D, Geldanamycin-Derived Cyclopentenone Macrolactams from an Eastern Kentucky Abandoned Coal Mine Microbe
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Xiachang Wang, Chang-Guo Zhan, Sherif I. Elshahawi, James C. Hower, Ziyuan Zhou, Jon S. Thorson, Yinan Zhang, Sean Parkin, Bruce E. Hatcher, M. Ryan Woodcock, Larissa V. Ponomareva, Madan K. Kharel, S. Randal Voss, Qingchao Qiu, Khaled A. Shaaban, and Xiabin Chen
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Cyclopentenone ,Stereochemistry ,Cell Survival ,Lactams, Macrocyclic ,Molecular Conformation ,Kentucky ,Cyclopentanes ,010402 general chemistry ,Streptomyces ,01 natural sciences ,Catalysis ,Article ,Benzilic acid rearrangement ,chemistry.chemical_compound ,Cell Line, Tumor ,Humans ,HSP90 Heat-Shock Proteins ,Cytotoxicity ,biology ,010405 organic chemistry ,Ansamycin ,Stereoisomerism ,General Chemistry ,General Medicine ,Geldanamycin ,biology.organism_classification ,Mycothiol ,0104 chemical sciences ,Coal ,chemistry ,Chemical engineering ,Biocatalysis - Abstract
Four cyclopentenone-containing ansamycin polyketides (mccrearamycins A-D), and six new geldanamycins (Gdms B-G, including new linear and mycothiol conjugates), were characterized as metabolites of Streptomyces sp. AD-23-14 isolated from the Rock Creek underground coal mine acid drainage site. Biomimetic chemical conversion studies using both simple synthetic models and Gdm D confirmed that the mccrearamycin cyclopentenone derives from benzilic acid rearrangement of 19-hydroxy Gdm, and thereby provides a new synthetic derivatization strategy and implicates a potential unique biocatalyst in mccrearamycin cyclopentenone formation. In addition to standard Hsp90α binding and cell line cytotoxicity assays, this study also highlights the first assessment of Hsp90α modulators in a new axolotl embryo tail regeneration (ETR) assay as a potential new whole animal assay for Hsp90 modulator discovery.
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- 2017
14. Spoxazomicin D and Oxachelin C, Potent Neuroprotective Carboxamides from the Appalachian Coal Fire-Associated Isolate Streptomyces sp. RM-14-6
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Xiachang Wang, James C. Hower, Manjula Sunkara, Mark A. Prendergast, Larissa V. Ponomareva, Matthew S. Tremblay, Gregory C. Copley, Yinan Zhang, Jianjun Zhang, Madan K. Kharel, Sherif I. Elshahawi, Meredith A. Saunders, Tuan Tran, Khaled A. Shaaban, Andrew J. Morris, and Jon S. Thorson
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Antifungal Agents ,Stereochemistry ,Pharmaceutical Science ,Coal fire ,010402 general chemistry ,01 natural sciences ,Streptomyces ,Neuroprotection ,Article ,Spoxazomicin D ,Analytical Chemistry ,Phenols ,Drug Discovery ,Humans ,Cytotoxicity ,Nuclear Magnetic Resonance, Biomolecular ,Oxazoles ,Pharmacology ,Appalachian Region ,Molecular Structure ,biology ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,biology.organism_classification ,Anti-Bacterial Agents ,0104 chemical sciences ,Sodium salt ,Coal ,Neuroprotective Agents ,Complementary and alternative medicine ,Biochemistry ,Unfolded protein response ,Molecular Medicine ,Peptides ,Oligopeptides ,Two-dimensional nuclear magnetic resonance spectroscopy ,Ethers - Abstract
The isolation and structure elucidation of six new bacterial metabolites [spoxazomicin D (2), oxachelins B and C (4, 5), and carboxamides 6–8] and 11 previously reported bacterial metabolites (1, 3, 9–12a, and 14–18) from Streptomyces sp. RM-14-6 is reported. Structures were elucidated on the basis of comprehensive 1D and 2D NMR and mass spectrometry data analysis, along with direct comparison to synthetic standards for 2, 11, and 12a,b. Complete 2D NMR assignments for the known metabolites lenoremycin (9) and lenoremycin sodium salt (10) were also provided for the first time. Comparative analysis also provided the basis for structural revision of several previously reported putative aziridine-containing compounds [exemplified by madurastatins A1, B1, C1 (also known as MBJ-0034), and MBJ-0035] as phenol-dihydrooxazoles. Bioactivity analysis [including antibacterial, antifungal, cancer cell line cytotoxicity, unfolded protein response (UPR) modulation, and EtOH damage neuroprotection] revealed 2 and 5 as potent neuroprotectives and lenoremycin (9) and its sodium salt (10) as potent UPR modulators, highlighting new functions for phenol-oxazolines/salicylates and polyether pharmacophores.
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- 2016
15. Jatrophacine, a 4,5-seco-rhamnofolane diterpenoid with potent anti-inflammatory activity from Jatropha curcas
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Lihong Hu, Yang Hu, Tu-Lin Lu, Qi Lv, Xiachang Wang, Huimin Zhao, Ning Ding, and Aiping Yang
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biology ,Traditional medicine ,010405 organic chemistry ,Chemistry ,medicine.drug_class ,Organic Chemistry ,Euphorbiaceae ,Plant Science ,biology.organism_classification ,01 natural sciences ,Biochemistry ,Terpenoid ,Anti-inflammatory ,0104 chemical sciences ,Analytical Chemistry ,010404 medicinal & biomolecular chemistry ,medicine ,Jatropha curcas - Abstract
A new diterpenoid named jatrophacine (1), with an unusual 4,5-seco- rhamnofolane skeleton, was isolated from the roots of Jatropha curcas, together with eleven known diterpenoids. The structure of the new compound was elucidated through a detailed analysis of its 1 D- and 2 D-NMR spectra. The X-ray structure of jatrophol (2) is also presented. Anti-inflammatory activity with LPS-induced RAW 264.7 macrophages revealed that compound 1 strongly inhibited the production of nitric oxide (IC50 = 0.53 μM).
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- 2019
- Full Text
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16. Puromycins B-E, Naturally Occurring Amino-Nucleosides Produced by the Himalayan Isolate Streptomyces sp. PU-14G
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Muhammad Abbas, Larissa V. Ponomareva, Imran Sajid, Xiachang Wang, Sherif I. Elshahawi, Jon S. Thorson, and Khaled A. Shaaban
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0301 basic medicine ,Stereochemistry ,Pharmaceutical Science ,Microbial Sensitivity Tests ,Gram-Positive Bacteria ,01 natural sciences ,Streptomyces ,Article ,Analytical Chemistry ,Mycobacterium ,03 medical and health sciences ,Drug Discovery ,Pakistan ,Pharmacology ,biology ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Nucleosides ,Isolation (microbiology) ,biology.organism_classification ,0104 chemical sciences ,030104 developmental biology ,Complementary and alternative medicine ,Molecular Medicine ,Puromycin - Abstract
The isolation and structure elucidation of four new naturally occurring amino-nucleoside [puromycins B-E (1-4)] metabolites from a Himalayan isolate ( Streptomyces sp. PU-14-G, isolated from the Bara Gali region of northern Pakistan) is reported. Consistent with prior reports, comparative antimicrobial assays revealed the need for the free 2″-amine for anti-Gram-positive bacteria and antimycobacterial activity. Similarly, comparative cancer cell line cytotoxicity assays highlighted the importance of the puromycin-free 2″-amine and the impact of 3'-nucleoside substitution. These studies extend the repertoire of known naturally occurring puromycins and their corresponding SAR. Notably, 1 represents the first reported naturally occurring bacterial puromycin-related metabolite with a 3'- N-amino acid substitution that differs from the 3'- N-tyrosinyl of classical puromycin-type natural products. This discovery suggests the biosynthesis of 1 in Streptomyces sp. PU-14G may invoke a uniquely permissive amino-nucleoside synthetase and/or multiple synthetases and sets the stage for further studies to elucidate, and potentially exploit, new biocatalysts for puromycin chemoenzymatic diversification.
- Published
- 2018
17. Frenolicin B Targets Peroxiredoxin 1 and Glutaredoxin 3 to Trigger ROS/4E-BP1-Mediated Antitumor Effects
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Yubin Guo, Larissa V. Ponomareva, Jing Chen, Luksana Chaiswing, Khaled A. Shaaban, Bradley D. Anderson, Jon S. Thorson, Markos Leggas, Xiachang Wang, Haining Zhu, Qiou Wei, Yanan Cao, Yinan Zhang, Qing Ye, Qing-Bai She, Jamie Horn, and Daret K. St. Clair
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Male ,Cell Survival ,Clinical Biochemistry ,Transplantation, Heterologous ,Mice, Nude ,Antineoplastic Agents ,Cell Cycle Proteins ,mTORC1 ,Biology ,Peroxiredoxin 1 ,Mechanistic Target of Rapamycin Complex 1 ,01 natural sciences ,Biochemistry ,Article ,chemistry.chemical_compound ,Mice ,Cell Line, Tumor ,Neoplasms ,Drug Discovery ,Animals ,Humans ,Phosphorylation ,RNA, Small Interfering ,Molecular Biology ,Protein kinase B ,Glutaredoxins ,Adaptor Proteins, Signal Transducing ,Pharmacology ,chemistry.chemical_classification ,Reactive oxygen species ,010405 organic chemistry ,Glutathione ,Peroxiredoxins ,0104 chemical sciences ,Cell biology ,chemistry ,Tumor progression ,Cancer cell ,Molecular Medicine ,RNA Interference ,Reactive Oxygen Species ,Naphthoquinones ,Signal Transduction - Abstract
Summary Peroxiredoxin 1 (Prx1) and glutaredoxin 3 (Grx3) are two major antioxidant proteins that play a critical role in maintaining redox homeostasis for tumor progression. Here, we identify the prototypical pyranonaphthoquinone natural product frenolicin B (FB) as a selective inhibitor of Prx1 and Grx3 through covalent modification of active-site cysteines. FB-targeted inhibition of Prx1 and Grx3 results in a decrease in cellular glutathione levels, an increase of reactive oxygen species (ROS), and concomitant inhibition of cancer cell growth, largely by activating the peroxisome-bound tuberous sclerosis complex to inhibit mTORC1/4E-BP1 signaling axis. FB structure-activity relationship studies reveal a positive correlation between inhibition of 4E-BP1 phosphorylation, ROS-mediated cancer cell cytotoxicity, and suppression of tumor growth in vivo. These findings establish FB as the most potent Prx1/Grx3 inhibitor reported to date and also notably highlight 4E-BP1 phosphorylation status as a potential predictive marker in response to ROS-based therapies in cancer.
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- 2018
18. Self-Resistance during Muraymycin Biosynthesis: a Complementary Nucleotidyltransferase and Phosphotransferase with Identical Modification Sites and Distinct Temporal Order
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Anke Lemke, Xiaodong Liu, Jon S. Thorson, Stefan Koppermann, Christian Ducho, Steven G. Van Lanen, Xiachang Wang, Jürgen Rohr, and Zheng Cui
- Subjects
0301 basic medicine ,Disaccharide ,Transferases (Other Substituted Phosphate Groups) ,Phosphotransferase ,03 medical and health sciences ,chemistry.chemical_compound ,Bacterial Proteins ,Biosynthesis ,Transferases ,Mechanisms of Resistance ,Gene cluster ,Translocase ,Pharmacology (medical) ,Nucleotide ,Phosphorylation ,Adenylylation ,Pharmacology ,chemistry.chemical_classification ,biology ,Nucleotides ,Phosphotransferases ,Nucleosides ,Nucleotidyltransferase ,Nucleotidyltransferases ,Streptomyces ,Anti-Bacterial Agents ,030104 developmental biology ,Infectious Diseases ,Biochemistry ,chemistry ,biology.protein ,Peptides - Abstract
Muraymycins are antibacterial natural products from Streptomyces spp. that inhibit translocase I (MraY), which is involved in cell wall biosynthesis. Structurally, muraymycins consist of a 5′- C -glycyluridine (GlyU) appended to a 5″-amino-5″-deoxyribose (ADR), forming a disaccharide core that is found in several peptidyl nucleoside inhibitors of MraY. For muraymycins, the GlyU-ADR disaccharide is further modified with an aminopropyl-linked peptide to generate the simplest structures, annotated as the muraymycin D series. Two enzymes encoded in the muraymycin biosynthetic gene cluster, Mur29 and Mur28, were functionally assigned in vitro as a Mg·ATP-dependent nucleotidyltransferase and a Mg·ATP-dependent phosphotransferase, respectively, both modifying the 3″-OH of the disaccharide. Biochemical characterization revealed that both enzymes can utilize several nucleotide donors as cosubstrates and the acceptor substrate muraymycin also behaves as an inhibitor. Single-substrate kinetic analyses revealed that Mur28 preferentially phosphorylates a synthetic GlyU-ADR disaccharide, a hypothetical biosynthetic precursor of muraymycins, while Mur29 preferentially adenylates the D series of muraymycins. The adenylated or phosphorylated products have significantly reduced (170-fold and 51-fold, respectively) MraY inhibitory activities and reduced antibacterial activities, compared with the respective unmodified muraymycins. The results are consistent with Mur29-catalyzed adenylation and Mur28-catalyzed phosphorylation serving as complementary self-resistance mechanisms, with a distinct temporal order during muraymycin biosynthesis.
- Published
- 2018
19. Bi- and Tetracyclic Spirotetronates from the Coal Mine Fire Isolate Streptomyces sp. LC-6-2
- Author
-
Xiachang Wang, James C. Hower, Jürgen Rohr, Steven G. Van Lanen, Khaled A. Shaaban, Gregory C. Copley, Sherif I. Elshahawi, Xiabin Chen, Chang-Guo Zhan, Yinan Zhang, Larissa V. Ponomareva, Sean Parkin, Wenlong Cai, and Jon S. Thorson
- Subjects
Stereochemistry ,Metabolite ,Molecular Conformation ,Pharmaceutical Science ,010402 general chemistry ,Crystallography, X-Ray ,01 natural sciences ,Streptomyces ,DNA sequencing ,Article ,Analytical Chemistry ,chemistry.chemical_compound ,Bridged Bicyclo Compounds ,Drug Discovery ,Gene cluster ,Spiro Compounds ,Nuclear Magnetic Resonance, Biomolecular ,Pharmacology ,biology ,Bicyclic molecule ,Molecular Structure ,010405 organic chemistry ,Extramural ,Organic Chemistry ,biology.organism_classification ,Bridged Bicyclo Compounds, Heterocyclic ,0104 chemical sciences ,Coal ,Complementary and alternative medicine ,chemistry ,Multigene Family ,Molecular Medicine ,Enantiomer - Abstract
The structures of 12 new “enantiomeric”-like abyssomicin metabolites (abyssomicins M–X) from Streptomyces sp. LC-6-2 are reported. Of this set, the abyssomicin W (11) contains an unprecedented 8/6/6/6 tetracyclic core, while the bicyclic abyssomicin X (12) represents the first reported naturally occurring linear spirotetronate. Metabolite structures were determined based on spectroscopic data and X-ray crystallography, and Streptomyces sp. LC-6-2 genome sequencing also revealed the corresponding putative biosynthetic gene cluster.
- Published
- 2017
20. Mullinamides A and B, New Cyclopeptides Produced by the Ruth Mullins Coal Mine Fire Isolate Streptomyces sp. RM-27-46
- Author
-
Madan K. Kharel, Jon S. Thorson, Gregory C. Copley, Manjula Sunkara, Khaled A. Shaaban, Sherif I. Elshahawi, Xiachang Wang, James C. Hower, Andrew J. Morris, and Larissa V. Ponomareva
- Subjects
Pharmacology ,natural product ,biology ,pharmacognosy ,Molecular Structure ,Stereochemistry ,bioprospecting ,surugamide ,Nuclear magnetic resonance spectroscopy ,Gene Expression Regulation, Bacterial ,biology.organism_classification ,Antimicrobial ,Streptomyces ,Coal Mining ,Peptides, Cyclic ,Article ,cyclopeptide ,antibiotic ,Drug Discovery ,lipids (amino acids, peptides, and proteins) ,Antibacterial activity - Abstract
Two new cyclopeptides, mullinamides A [cyclo-(-l-Gly-l-Glu-l-Val-l-Ile-l-Pro-)] and B [cyclo-(-l-Glu-l-Met-l-Pro-)] were isolated from the crude extract of terrestrial Streptomyces sp. RM-27-46 along with the three known cyclopeptides surugamide A [cyclo-(-l-Ile-d-Ile-l-Lys-l-Ile-d-Phe-d-Leu-l-Ile-d-Ala-)], cyclo-(-l-Pro-l-Phe-) and cyclo-(-l-Pro-l-Leu-). The structures of the new compounds were elucidated by the cumulative analyses of NMR spectroscopy and high resolution mass spectrometry. While mullinamides A and B displayed no appreciable antimicrobial/fungal activity or cytotoxicity, this study highlights the first reported antibacterial activity of surugamide A.
- Published
- 2014
21. Venturicidin C, A New 20-Membered Macrolide Produced by Streptomyces sp. TS-2-2
- Author
-
Xiachang Wang, Manjula Sunkara, James C. Hower, Khaled A. Shaaban, Jon S. Thorson, Andrew J. Morris, Gregory C. Copley, Sherif I. Elshahawi, Madan K. Kharel, Larissa V. Ponomareva, and Shanteri Singh
- Subjects
Antifungal ,microbial ,Antifungal Agents ,Lung Neoplasms ,Magnetic Resonance Spectroscopy ,Stereochemistry ,medicine.drug_class ,natural products ,secondary metabolite ,Ferrioxamine E ,Streptomyces ,Peptides, Cyclic ,Article ,Mass Spectrometry ,Venturicidin C ,Cell Line, Tumor ,Drug Discovery ,medicine ,apoptolidin ,Humans ,Streptomycetes ,Pharmacology ,biology ,Chemistry ,Nuclear magnetic resonance spectroscopy ,biology.organism_classification ,Adenosine ,3. Good health ,Cell culture ,Venturicidins ,Macrolides ,medicine.drug - Abstract
Venturicidin C (1), a new 20-membered macrolide along with the known venturicidins A (2) and B (3) were isolated from the crude extract of the Appalachian bacterial strain Streptomyces sp. TS-2-2. Additionally, nine other known compounds namely nocardamine, dehydroxynocardamine, desmethylenlnocardamine, ferrioxamine E (FOE), adenosine, riboflavin, cyclo(d)-trans-4-OH-Pro-(d)-Phe, cyclo(d)-Pro-(d)-Phe, and N-(2-phenylethyl)-acetamide were also isolated and identified. The structure of the new macrolide 1 was elucidated by the cumulative analyses of NMR and HR-MS spectrometry data. Complete NMR assignments for the known venturicidins A (2) and B (3) are also provided, for the first time, in this report. Venturicidins A-C did not inhibit the proliferation of A549 lung cancer cell lines but all displayed potent antifungal activity.
- Published
- 2013
22. Three new lupane-type triterpenes from Ceriops tagal
- Author
-
Xiao-Wei Ouyang, Lihong Hu, and Xiachang Wang
- Subjects
Stereochemistry ,Plant composition ,Pharmaceutical Science ,Analytical Chemistry ,Terpene ,Triterpenoid ,Ceriops tagal ,Triterpene ,Drug Discovery ,Botany ,Spectral analysis ,Nuclear Magnetic Resonance, Biomolecular ,Pharmacology ,chemistry.chemical_classification ,Molecular Structure ,biology ,Chemistry ,Organic Chemistry ,Rhizophoraceae ,General Medicine ,biology.organism_classification ,Triterpenes ,Terpenoid ,Complementary and alternative medicine ,Molecular Medicine ,Drugs, Chinese Herbal - Abstract
Three new lupane-type triterpenes, 3 alpha-O-trans-feruloylbetulinic acid (1), 3 alpha-O-trans-coumaroylbetulinic acid (2) and 3beta-O-cis-feruloylbetulin (3), together with 10 known triterpenes (4-13), were isolated from the aerial parts of the mangrove plant Ceriops tagal. The structures of the three new compounds were established by means of spectroscopic data analyses and chemical methods.
- Published
- 2010
23. A New Diterpenoid and a New Diterpenoid Alkaloid fromAconitum coreanum
- Author
-
Jing-Han Liu, Wen-Ying Liu, Xiachang Wang, Chunhua Yang, and Qingfa Tang
- Subjects
Traditional medicine ,biology ,Chemistry ,Alkaloid ,Organic Chemistry ,biology.organism_classification ,Biochemistry ,Catalysis ,Terpenoid ,Aconitum coreanum ,Inorganic Chemistry ,Drug Discovery ,Medicinal herbs ,Physical and Theoretical Chemistry ,Guan - Abstract
A new diterpenoid, guan fu diterpenoid A (1), and a new diterpenoid alkaloid, guan fu base S (2), were isolated from the Chinese medicinal herb Aconitum coreanum (Levl.) Rapaics, together with five known diterpenoid alkaloids guan fu base P, guan fu base R, guan fu base G, guan fu base F, and guan fu base Z. The structures of the two new compounds were elucidated as ent-kaurane-16,20-diol (1) and (11β,13S)-2,3,15,16-tetradehydro-16,17-dihydrohetisan-11,13,14-triol 11,13-diacetate (2) on the basis of HR-MS and 2D-NMR analyses. This is the first report of an ent-kaurane diterpenoid in Aconitum coreanum.
- Published
- 2008
24. Lindenane Sesquiterpene Dimers from Chloranthus fortunei
- Author
-
Lihong Hu, Jing-Han Liu, Li-Li Wang, Xiachang Wang, Shi-Ping Ma, and Yinan Zhang
- Subjects
Stereochemistry ,Dimer ,Pharmaceutical Science ,Sesquiterpene ,Plant Roots ,Analytical Chemistry ,Magnoliopsida ,chemistry.chemical_compound ,Polycyclic compound ,Drug Discovery ,Organic chemistry ,Nuclear Magnetic Resonance, Biomolecular ,Pharmacology ,chemistry.chemical_classification ,Molecular Structure ,biology ,Organic Chemistry ,Absolute configuration ,biology.organism_classification ,Terpenoid ,Complementary and alternative medicine ,chemistry ,Molecular Medicine ,Sesquiterpenes ,Two-dimensional nuclear magnetic resonance spectroscopy ,Chloranthaceae ,Lactone ,Drugs, Chinese Herbal - Abstract
Five new lindenane sesquiterpene dimers ( 1- 5), named shizukaols K-O, and eight known sesquiterpene dimers were isolated from the roots of Chloranthus fortunei. The structures of 1- 5 were elucidated using spectroscopic data, mainly 1D NMR, 2D NMR, and mass spectra.
- Published
- 2008
25. Cytotoxic Indolocarbazoles from Actinomadura melliaura ATCC 39691
- Author
-
Xiachang Wang, Jon S. Thorson, Khaled A. Shaaban, Madan K. Kharel, Markos Leggas, Sherif I. Elshahawi, and Jamie Horn
- Subjects
Staphylococcus aureus ,Stereochemistry ,Metabolite ,Mycobacterium smegmatis ,Carbazoles ,Pharmaceutical Science ,Microbial Sensitivity Tests ,Saccharomyces cerevisiae ,Alkylation ,Biology ,Article ,California ,Analytical Chemistry ,Indole Alkaloids ,chemistry.chemical_compound ,Drug Discovery ,Actinomycetales ,Potency ,Humans ,Nuclear Magnetic Resonance, Biomolecular ,Soil Microbiology ,ADME ,Pharmacology ,Antibiotics, Antineoplastic ,Strain (chemistry) ,Molecular Structure ,Organic Chemistry ,Methylation ,Carbon-13 NMR ,Micrococcus luteus ,Complementary and alternative medicine ,Biochemistry ,chemistry ,Molecular Medicine ,Topoisomerase I Inhibitors ,Two-dimensional nuclear magnetic resonance spectroscopy - Abstract
Actinomadura melliaura ATCC 39691, a strain isolated from a soil sample collected in Bristol Cove, California, is a known producer of the disaccharide-substituted AT2433 indolocarbazoles (6-9). Reinvestigation of this strain using new media conditions led to40-fold improvement in the production of previously reported AT2433 metabolites and the isolation and structure elucidation of the four new analogues, AT2433-A3, A4, A5, and B3 (1-4). The availability of this broader set of compounds enabled a subsequent small antibacterial/fungal/cancer SAR study that revealed disaccharyl substitution, N-6 methylation, and C-11 chlorination as key modulators of bioactivity. The slightly improved anticancer potency of the newly reported N-6-desmethyl 1 (compared to 6) contrasts extensive SAR of monoglycosylated rebeccamycin-type topoisomerase I inhibitors where N-6 alkylation has contributed to improved potency and ADME. Complete 2D NMR assignments for the known metabolite BMY-41219 (5) and (13)C NMR spectroscopic data for the known analogue AT2433-B1 (7) are also provided for the first time.
- Published
- 2015
26. Terfestatins B and C, New p-Terphenyl Glycosides Produced by Streptomyces sp. RM-5–8
- Author
-
Mark A. Prendergast, Xiachang Wang, James C. Hower, Gregory C. Copley, Khaled A. Shaaban, Andrew J. Morris, Ibrahim S. Elgumati, Anna R. Reynolds, Manjula Sunkara, Madan K. Kharel, Steven G. Van Lanen, Yinan Zhang, Sherif I. Elshahawi, Larissa V. Ponomareva, Jon S. Thorson, and Meredith A. Saunders
- Subjects
Stereochemistry ,Biochemistry ,Streptomyces ,Article ,chemistry.chemical_compound ,Glucuronides ,Glucosides ,Terphenyl ,Terphenyl Compounds ,Animals ,Glycosides ,Physical and Theoretical Chemistry ,chemistry.chemical_classification ,biology ,Molecular Structure ,Hexuronic Acids ,Organic Chemistry ,Glycoside ,Rare sugar ,biology.organism_classification ,Rats ,chemistry ,Cell culture - Abstract
Terfestatins B (1) and C (2), new p-terphenyls bearing a novel unsaturated hexuronic acid (4-deoxy-α-l-threo-hex-4-enopyranuronate), a unique β-d-glycosyl ester of 5-isoprenylindole-3-carboxylate (3) and the same rare sugar, and two new hygromycin precursors, were characterized as metabolites of the coal mine fire isolate Streptomyces sp. RM-5–8. EtOH damage neuroprotection assays using rat hippocampal-derived primary cell cultures with 1, 2, 3 and echoside B (a terfestatin C-3′-β-d-glucuronide from Streptomyces sp. RM-5– 8) revealed 1 as potently neuroprotective, highlighting a new potential application of the terfestatin scaffold.
- Published
- 2015
27. Ruthmycin, a new tetracyclic polyketide from Streptomyces sp. RM-4-15
- Author
-
Yinan Zhang, Jon S. Thorson, Lei Fang, Gregory C. Copley, Sherif I. Elshahawi, Madan K. Kharel, Larissa V. Ponomareva, Chang-Guo Zhan, Xiachang Wang, James C. Hower, and Khaled A. Shaaban
- Subjects
Antifungal ,Six member ,Antifungal Agents ,biology ,Molecular Structure ,medicine.drug_class ,Chemistry ,Stereochemistry ,Organic Chemistry ,Kentucky ,Microbial Sensitivity Tests ,biology.organism_classification ,Biochemistry ,Streptomyces ,Article ,Polyketide ,Frenolicin ,Polyketides ,medicine ,Physical and Theoretical Chemistry ,Nuclear Magnetic Resonance, Biomolecular ,Bacteria ,Naphthoquinones - Abstract
The isolation and structural elucidation of a new tetracyclic polyketide (ruthmycin) from Streptomyces sp. RM-4-15, a bacteria isolated near thermal vents from the Ruth Mullins underground coal mine fire in eastern Kentucky, is reported. In comparison to the well-established frenolicin core scaffold, ruthmycin possesses an unprecedented signature C3 bridge and a corresponding fused six member ring. Preliminary in vitro antibacterial, anticancer, and antifungal assays revealed ruthmycin to display moderate antifungal activity.
- Published
- 2013
28. The native production of the sesquiterpene isopterocarpolone by Streptomyces sp. RM-14-6
- Author
-
Gregory C. Copley, Shanteri Singh, Sherif I. Elshahawi, Khaled A. Shaaban, Andrew J. Morris, Madan K. Kharel, Jon S. Thorson, Larissa V. Ponomareva, Xiachang Wang, James C. Hower, and Manjula Sunkara
- Subjects
Spectrometry, Mass, Electrospray Ionization ,biology ,Molecular Structure ,Metabolite ,Organic Chemistry ,Context (language use) ,Plant Science ,Naphthols ,biology.organism_classification ,Sesquiterpene ,Biochemistry ,Streptomyces ,Geosmin ,Terpenoid ,Article ,Analytical Chemistry ,chemistry.chemical_compound ,chemistry ,Biosynthesis ,Two-dimensional nuclear magnetic resonance spectroscopy ,Nuclear Magnetic Resonance, Biomolecular ,Sesquiterpenes - Abstract
We report the production, isolation and structure elucidation of the sesquiterpene isopterocarpolone from an Appalachian isolate Streptomyces species RM-14-6. While isopterocarpolone was previously put forth as a putative plant metabolite, the current study highlights the first native bacterial production of isopterocarpolone and the first full characterization of isopterocarpolone using 1D and 2D NMR spectroscopy and HR-ESI mass spectrometry. Considering the biosynthesis of closely related metabolites (geosmin or 5-epiaristolochene), the structure of isopterocarpolone also suggests the potential participation of one or more unique enzymatic transformations. In this context, this work also sets the stage for the elucidation of potentially novel bacterial biosynthetic machinery.
- Published
- 2013
29. Herbimycins D-F, ansamycin analogues from Streptomyces sp. RM-7-15
- Author
-
Khaled A. Shaaban, Andrew J. Morris, Manjula Sunkara, Jon S. Thorson, Madan K. Kharel, Sherif I. Elshahawi, Gregory C. Copley, Xiachang Wang, James C. Hower, and Larissa V. Ponomareva
- Subjects
Staphylococcus aureus ,Stereochemistry ,Cell Survival ,Electrospray ionization ,Saccharomyces cerevisiae ,Pharmaceutical Science ,Context (language use) ,Microbial Sensitivity Tests ,Biology ,medicine.disease_cause ,Streptomyces ,Article ,Analytical Chemistry ,Microbiology ,Drug Discovery ,medicine ,Humans ,HSP90 Heat-Shock Proteins ,Cytotoxicity ,Nuclear Magnetic Resonance, Biomolecular ,Pharmacology ,Ansamycin ,Organic Chemistry ,Salmonella enterica ,biology.organism_classification ,Antimicrobial ,Anti-Bacterial Agents ,Complementary and alternative medicine ,Rifabutin ,Molecular Medicine - Abstract
Bacterial strains belonging to the class actinomycetes were isolated from the soil near a thermal vent of the Ruth Mullins coal fire (Appalachian mountains of Eastern Kentucky). High resolution electrospray ionization mass spectrometry (HR-ESI-MS) and ultraviolet (UV) absorption profiles of metabolites from one of the isolates (Streptomyces sp. RM-7-15) revealed the presence of a unique set of metabolites ultimately determined to be herbimycins D-F (1–3). In addition, herbimycin A (4), dihydroherbimycin A (TAN 420E) (7), and the structurally distinct antibiotic bicycylomycin were isolated from the crude extract of Streptomyces sp. RM-7-15. Herbimycins A, D-F (1–3) displayed comparable binding affinities to the Hsp90α. While the new analogues were found to be inactive in cancer cell cytotoxicity and antimicrobial assays, they may offer new insights in the context of non-toxic ansamycin-based Hsp90 inhibitors for the treatment of neurodegenerative disease.
- Published
- 2013
30. Frenolicins C-G, pyranonaphthoquinones from Streptomyces sp. RM-4-15
- Author
-
Yinan Zhang, Manjula Sunkara, Sherif I. Elshahawi, Khaled A. Shaaban, Jon S. Thorson, Andrew J. Morris, Xiachang Wang, James C. Hower, Madan K. Kharel, Gregory C. Copley, and Larissa V. Ponomareva
- Subjects
Frenolicin B ,Spectrometry, Mass, Electrospray Ionization ,Stereochemistry ,Electrospray ionization ,Pharmaceutical Science ,Streptomyces ,Article ,Analytical Chemistry ,chemistry.chemical_compound ,Structure-Activity Relationship ,Drug Discovery ,Organic chemistry ,Humans ,Scandium chloride ,Pharmacology ,Appalachian Region ,Natural product ,biology ,Strain (chemistry) ,Molecular Structure ,Chemistry ,Organic Chemistry ,Chemical modification ,biology.organism_classification ,Actinobacteria ,Complementary and alternative medicine ,Pyrones ,Molecular Medicine ,Fermentation ,Drug Screening Assays, Antitumor ,Naphthoquinones - Abstract
Appalachian active coal fire sites were selected for the isolation of bacterial strains belonging to the class actinobacteria. A comparison of high resolution electrospray ionization mass spectrometry (HR-ESI-MS) and ultraviolet (UV) absorption profiles from isolate extracts to natural product databases suggested Streptomyces sp. RM-4-15 to produce unique metabolites. Four new pyranonaphthoquinones, frenolicins C–F (1–4), along with three known analogues, frenolicin (6), frenolicin B (7), and UCF76-A (8), were isolated from the fermentation of this strain. An additional new analogue frenolicin G (5) along with two known compounds, deoxyfrenolicin (9) and UCF 13 (10), were isolated from the fermentation supplied with 18 mg/L of scandium chloride - the first example, to the best of our knowledge, wherein scandium chloride supplementation led to the confirmed production of new bacterial secondary metabolites. Structures 1–5 were elucidated on the basis of spectral analysis and chemical modification. While frenolicins are best known for their anticoccidial activity, the current study revealed compounds 6–9 to exhibit moderate cytotoxicity against the human lung carcinoma cell line (A549) and thereby extends the anticancer SAR for this privileged scaffold.
- Published
- 2013
31. ChemInform Abstract: Jatrophalactam, a Novel Diterpenoid Lactam Isolated from Jatropha curcas
- Author
-
Lihong Hu, Zong-Ping Zheng, Xianwen Gan, and Xiachang Wang
- Subjects
Terpene ,chemistry.chemical_compound ,biology ,Chemistry ,Stereochemistry ,Lactam ,General Medicine ,biology.organism_classification ,Jatropha curcas ,Terpenoid - Abstract
Jatrophalactam (1), a novel diterpenoid lactam possessing an unprecedented 5/13/3 tricyclic skeleton, was isolated from the roots of Jatropha curcas. The structure and relative configuration of jatrophalactam (1) were elucidated by extensive spectroscopic analysis and further determined by a single-crystal X-ray diffraction.
- Published
- 2010
32. Tyrosinase inhibitory constituents from the roots of Morus nigra: a structure-activity relationship study
- Author
-
Zong-Ping Zheng, Zhi-Xiu Lin, Mingfu Wang, Ka-Wing Cheng, Qin Zhu, and Xiachang Wang
- Subjects
Mulberrofuran G ,Mulberroside A ,biology ,Traditional medicine ,Monophenol Monooxygenase ,Plant Extracts ,Tyrosinase ,General Chemistry ,biology.organism_classification ,Plant Roots ,Oxyresveratrol ,chemistry.chemical_compound ,Structure-Activity Relationship ,chemistry ,Phytochemical ,Biochemistry ,biology.protein ,Morus ,Enzyme Inhibitors ,General Agricultural and Biological Sciences ,Catechol oxidase ,Kojic acid ,Morus nigra - Abstract
The phytochemical profiles of Morus nigra roots and twigs were compared by HPLC with those of the old and young twigs of Morus alba which are known to contain oxyresveratrol and mulberroside A as major components. It was found that M. nigra root extract contains some unknown natural products with potential tyrosinase inhibitory activity. The extract (95% ethanol) of the roots of M. nigra was further investigated in this study. One new compound, 5'-geranyl-5,7,2',4'-tetrahydroxyflavone, and twenty-eight known phenolic compounds were isolated. Their structures were identified by mass spectrometry and NMR spectroscopy. Nine compounds, 5'-geranyl-5,7,2',4'-tetrahydroxyflavone, steppogenin-7-O-beta-D-glucoside, 2,4,2',4'-tetrahydroxychalcone, moracin N, kuwanon H, mulberrofuran G, morachalcone A, oxyresveratrol-3'-O-beta-D-glucopyranoside and oxyresveratrol-2-O-beta-D-glucopyranoside, showed better tyrosinase inhibitory activities than kojic acid. It was noteworthy that the IC(50) values of 2,4,2',4'-tetrahydroxychalcone and morachalcone A were 757-fold and 328-fold lower than that of kojic acid, respectively, suggesting a great potential for their development as effective natural tyrosinase inhibitors.
- Published
- 2010
33. Jatrophalactam, a novel diterpenoid lactam isolated from Jatropha curcas
- Author
-
Zong-Ping Zheng, Lihong Hu, Xiachang Wang, and Xianwen Gan
- Subjects
biology ,Lactams ,Molecular Structure ,Chemistry ,Stereochemistry ,Organic Chemistry ,Molecular Conformation ,Jatropha ,biology.organism_classification ,Crystallography, X-Ray ,Biochemistry ,Plant Roots ,Terpenoid ,chemistry.chemical_compound ,Lactam ,Humans ,Physical and Theoretical Chemistry ,Diterpenes ,Drug Screening Assays, Antitumor ,Jatropha curcas ,Nuclear Magnetic Resonance, Biomolecular - Abstract
Jatrophalactam (1), a novel diterpenoid lactam possessing an unprecedented 5/13/3 tricyclic skeleton, was isolated from the roots of Jatropha curcas. The structure and relative configuration of jatrophalactam (1) were elucidated by extensive spectroscopic analysis and further determined by a single-crystal X-ray diffraction.
- Published
- 2009
34. Chemical components and tyrosinase inhibitors from the twigs of Artocarpus heterophyllus
- Author
-
Zong-Ping Zheng, Mingfu Wang, Jiajun Wu, Xiachang Wang, Ka-Wing Cheng, Sibao Chen, Shi-Yun Wang, and Dajiang Yang
- Subjects
chemistry.chemical_classification ,Chromatography ,biology ,Monophenol Monooxygenase ,Plant Extracts ,Tyrosinase ,General Chemistry ,Moraceae ,biology.organism_classification ,High-performance liquid chromatography ,Plant Roots ,Fungal Proteins ,chemistry.chemical_compound ,Artocarpus ,Enzyme ,chemistry ,Dihydromorin ,Plant Bark ,Organic chemistry ,Phenols ,General Agricultural and Biological Sciences ,Kojic acid ,Agaricales ,Peptides - Abstract
An HPLC method was developed and validated to compare the chemical profiles and tyrosinase inhibitors in the woods, twigs, roots, and leaves of Artocarpus heterophyllus . Five active tyrosinase inhibitors including dihydromorin, steppogenin, norartocarpetin, artocarpanone, and artocarpesin were used as marker compounds in this HPLC method. It was discovered that the chemical profiles of A. heterophyllus twigs and woods are quite different. Systematic chromatographic methods were further applied to purify the chemicals in the twigs of A. heterophyllus. Four new phenolic compounds, including one isoprenylated 2-arylbenzofuran derivative, artoheterophyllin A (1), and three isoprenylated flavonoids, artoheterophyllin B (2), artoheterophyllin C (3), and artoheterophyllin D (4), together with 16 known compounds, were isolated from the ethanol extract of the twigs of A. heterophyllus. The structures of compounds 1-4 were elucidated by spectroscopic analysis. However, the four new compounds did not show significant inhibitory activities against mushroom tyrosinase compared to kojic acid. It was found that similar compounds, such as norartocarpetin and artocarpesin in the twigs and woods of A. heterophyllus, contributed to their tyrosinase inhibitory activity.
- Published
- 2009
35. Correction to 'Terfestatins B and C, New p-Terphenyl Glycosides Produced by Streptomyces sp. RM-5–8'
- Author
-
Xiachang Wang, James C. Hower, Mark A. Prendergast, Jon S. Thorson, Anna R. Reynolds, Gregory C. Copley, Manjula Sunkara, Khaled A. Shaaban, Yinan Zhang, Andrew J. Morris, Sherif I. Elshahawi, Madan K. Kharel, Steven G. Van Lanen, Meredith A. Saunders, Ibrahim S. Elgumati, and Larissa V. Ponomareva
- Subjects
chemistry.chemical_classification ,chemistry.chemical_compound ,biology ,Chemistry ,Stereochemistry ,Terphenyl ,Organic Chemistry ,Glycoside ,Physical and Theoretical Chemistry ,biology.organism_classification ,Biochemistry ,Streptomyces - Published
- 2015
36. A New Dolabrane-type Diterpene from Ceriops tagal
- Author
-
Xiao-Wei Ouyang, Lihong Hu, Qing-Xi Yue, and Xiachang Wang
- Subjects
Pharmacology ,biology ,Stereochemistry ,Plant composition ,Rhizophoraceae ,Plant Science ,General Medicine ,biology.organism_classification ,HeLa ,chemistry.chemical_compound ,Complementary and alternative medicine ,chemistry ,Ceriops tagal ,Drug Discovery ,Botany ,Cervical carcinoma ,Diterpene ,Cancer cell lines - Abstract
A new dolabrane-type diterpene named tagalsin O 1, together with six known analogues 2-7, were isolated from the aerial part of the mangrove plant Ceriops tagal. The structures and relative configurations were elucidated on the basis of their spectroscopic data. Cytotoxicity of the isolated compounds against HeLa human cervical carcinoma cancer cell line was evaluated.
- Published
- 2010
37. Guaiane Sesquiterpenoids from Jatropha curcas
- Author
-
Lihong Hu, Jing-Han Liu, Xiachang Wang, and Shi-Ping Ma
- Subjects
Pharmacology ,biology ,Chemistry ,Chemical structure ,Plant composition ,Plant Science ,General Medicine ,biology.organism_classification ,Complementary and alternative medicine ,Drug Discovery ,Botany ,Medicinal plants ,Chemical composition ,Jatropha curcas - Abstract
Two new guaiane sesquiterpenoids named jatrophaols A and B (1, 2), along with three known analogues, were isolated from the roots of Jatropha curcas. Their structures were determined by spectroscopic methods, including 1D and 2D NMR spectroscopy, HR-EI-MS, HR-ESI-MS, and X-ray diffraction, as well as by comparison of their spectral data with those of related compounds.
- Published
- 2008
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