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1.
Chem Commun (Camb) ; 57(97): 13174-13177, 2021 Dec 07.
Article in English | MEDLINE | ID: mdl-34812827

ABSTRACT

A new Mtb fluorescent probe, NFC-Tre-5, was reported that could label single cells of Mtb under various stress conditions via a unique fluorescence off-on feature by a Rv2466c-mediated reductive mechanism. This probe effectively facilitates the rapid and specific detection of Mtb in the host cell during infection and the detection of Mtb in sputum samples from patients.


Subject(s)
Fluorescent Dyes/chemistry , Mycobacterium tuberculosis/isolation & purification , Nitroreductases/metabolism , Pyranocoumarins/chemistry , Trehalose/chemistry , Fluorescent Dyes/metabolism , Humans , Molecular Structure , Pyranocoumarins/metabolism , Sputum/microbiology , Trehalose/metabolism
2.
Molecules ; 25(21)2020 Oct 28.
Article in English | MEDLINE | ID: mdl-33126458

ABSTRACT

Calanolides are tetracyclic 4-substituted dipyranocoumarins. Calanolide A, isolated from the leaves and twigs of Calophyllum lanigerum var. austrocoriaceum (Whitmore) P. F. Stevens, is the first member of this group of compounds with anti-HIV-1 activity mediated by reverse transcriptase inhibition. Calanolides are classified pharmacologically as non-nucleoside reverse transcriptase inhibitors (NNRTI). There are at least 15 naturally occurring calanolides distributed mainly within the genus Calophyllum, but some of them are also present in the genus Clausena. Besides significant anti-HIV properties, which have been exploited towards potential development of new NNRTIs for anti-HIV therapy, calanolides have also been found to possess anticancer, antimicrobial and antiparasitic potential. This review article provides a comprehensive update on all aspects of naturally occurring calanolides, including their chemistry, natural occurrence, biosynthesis, pharmacological and toxicological aspects including mechanism of action and structure activity relationships, pharmacokinetics, therapeutic potentials and available patents.


Subject(s)
Biological Products/metabolism , Biological Products/pharmacology , Pyranocoumarins/metabolism , Pyranocoumarins/pharmacology , Biological Products/chemistry , Biological Products/therapeutic use , Humans , Pyranocoumarins/chemistry , Pyranocoumarins/therapeutic use
3.
ACS Synth Biol ; 9(9): 2282-2290, 2020 09 18.
Article in English | MEDLINE | ID: mdl-32786357

ABSTRACT

Natural products containing benzoheterocyclic skeletons are widely found in plants and exhibit various pharmacological activities. To address the current limited availability of these compounds, we herein demonstrate the production of benzopyran, furanocoumarins, and pyranocoumarins in Streptomyces xiamenensis by employing prenyltransferases and two substrate-promiscuous enzymes, XimD and XimE. To avoid the degradation in S. xiamenensis, furanocoumarins and pyranocoumarins were also successfully produced in Escherichia coli. The production of linear furanocoumarins (marmesin) and angular pyranocoumarins (decursinol) reached 3.6 and 3.7 mg/L in shake flasks, respectively. To the best of our knowledge, this is the first report of the microbial production of the plant metabolites furanocoumarins and pyranocoumarins. Our study complements the missing link in the biosynthesis of pyranocoumarins by leveraging the catalytic promiscuity of microbial enzymes.


Subject(s)
Heterocyclic Compounds/chemistry , Streptomyces/metabolism , Benzopyrans/chemistry , Benzopyrans/metabolism , Biocatalysis , Biological Products/chemistry , Biological Products/metabolism , Dimethylallyltranstransferase/genetics , Dimethylallyltranstransferase/metabolism , Escherichia coli/chemistry , Escherichia coli/metabolism , Furocoumarins/biosynthesis , Furocoumarins/chemistry , Genetic Engineering , Heterocyclic Compounds/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Pyranocoumarins/chemistry , Pyranocoumarins/metabolism , Streptomyces/chemistry , Streptomyces/genetics , Substrate Specificity
4.
J Nat Prod ; 83(5): 1409-1415, 2020 05 22.
Article in English | MEDLINE | ID: mdl-32372647

ABSTRACT

Citrus sinensis and Citrus limonia were obtained by germination from seeds, and isotopic-labeling experiments using d-[1-13C]glucose were performed with the seedlings. After 60 days, the seedlings were analyzed by high-performance liquid chromatography-ultraviolet-solid-phase extraction-nuclear magnetic resonance, data and the 13C enrichment patterns of xanthyletin and seselin indicated that the pyran ring was formed by the methylerythritol phosphate pathway and that the coumarin moiety was derived from the shikimate pathway in both compounds. This information regarding the biosynthetic pathway can be used to increase resistance against phytopathogens, because xanthyletin and seselin are reported to have antimicrobial activity on the growth of Xylella fastidiosa, which causes citrus variegated chlorosis in orange.


Subject(s)
Isotope Labeling/methods , Pyranocoumarins/metabolism , Carbon Isotopes , Chromatography, High Pressure Liquid , Citrus/metabolism , Citrus sinensis/metabolism , Magnetic Resonance Spectroscopy , Molecular Structure , Plant Diseases/microbiology , Pyranocoumarins/chemistry , Pyranocoumarins/isolation & purification , Shikimic Acid/metabolism , Solid Phase Extraction , Spectrophotometry, Ultraviolet , Xylella/drug effects
5.
Molecules ; 22(12)2017 Dec 07.
Article in English | MEDLINE | ID: mdl-29215592

ABSTRACT

Angelica gigas Nakai (AGN) is a crucial oriental medicinal herb that grows especially in Korea and the Far-East countries. It contains chemically active compounds like pyranocoumarins, polyacetylenes and essential oils, which might be useful for treatment of several chronic diseases. It has been used for centuries as a traditional medicine in Southeast Asia, but in Western countries is used as a functional food and a major ingredient of several herbal products. The genus Angelica is also known as 'female ginseng' due to its critical therapeutic role in female afflictions, such as gynecological problems. However, it is well-documented that the AGN pyranocoumarins may play vital beneficial roles against cancer, neurodisorders, inflammation, osteoporosis, amnesia, allergies, depression, fungi, diabetes, ischemia, dermatitis, reactive oxygen species (ROS) and androgen. Though numerous studies revealed the role of AGN pyranocoumarins as therapeutic agents, none of the reviews have published their molecular mechanism of action. To the best of our knowledge, this would be the first review that aims to appraise the biosynthesis of AGN's major active pyranocoumarins, discuss effective extraction and formulation methods, and detail the molecular action mechanism of decursin (D), decursinol angelate (DA) and decursinol (DOH) in chronic diseases, which would further help extension of research in this area.


Subject(s)
Angelica/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Drugs, Chinese Herbal/pharmacology , Neoplasms/drug therapy , Phytotherapy/methods , Pyranocoumarins/pharmacology , Angelica sinensis , Animals , Antineoplastic Agents, Phytogenic/biosynthesis , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacokinetics , Benzopyrans/isolation & purification , Benzopyrans/metabolism , Benzopyrans/pharmacokinetics , Benzopyrans/pharmacology , Butyrates/isolation & purification , Butyrates/metabolism , Butyrates/pharmacokinetics , Butyrates/pharmacology , Disease Models, Animal , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacokinetics , Humans , Liquid-Liquid Extraction/methods , Medicine, Korean Traditional , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/pathology , Plant Extracts/chemistry , Plant Roots/chemistry , Plants, Medicinal , Pyranocoumarins/isolation & purification , Pyranocoumarins/metabolism , Pyranocoumarins/pharmacokinetics , Rodentia
6.
Am J Chin Med ; 45(8): 1773-1792, 2017.
Article in English | MEDLINE | ID: mdl-29121805

ABSTRACT

We have previously shown that the ethanol extract of dried Angelica gigas Nakai (AGN) root exerts anticancer activity against androgen receptor (AR)-negative human DU145 and PC-3 prostate cancer xenografts and primary carcinogenesis in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. The major pyranocoumarin isomers decursin (D) and decursinol angelate (DA), when provided at equi-molar intake to that provided by AGN extract, accounted for the inhibitory efficacy against precancerous epithelial lesions in TRAMP mice. Since we and others have shown in rodents and humans that D and DA rapidly and extensively convert to decursinol, here we tested whether decursinol might be an in vivo active compound for suppressing xenograft growth of human prostate cancer cells expressing AR. In SCID-NSG mice carrying subcutaneously inoculated human LNCaP/AR-Luc cells overexpressing the wild type AR, we compared the efficacy of 4.5[Formula: see text]mg decursinol per mouse with equi-molar dose of 6[Formula: see text]mg D/DA per mouse. The result showed that decursinol decreased xenograft tumor growth by 75% and the lung metastasis, whereas D/DA exerted a much less effect. Measurement of plasma decursinol concentration, at 3[Formula: see text]h after the last dose of respective dosing regimen, showed higher circulating level in the decursinol-treated NSG mice than in the D/DA-treated mice. In a subsequent single-dose pharmacokinetic experiment, decursinol dosing led to 3.7-fold area under curve (AUC) of plasma decursinol over that achieved by equi-molar D/DA dosing. PK advantage notwithstanding, decursinol represents an active compound to exert in vivo prostate cancer growth and metastasis inhibitory activity in the preclinical model.


Subject(s)
Adenocarcinoma/pathology , Angelica/chemistry , Antineoplastic Agents, Phytogenic , Benzopyrans/pharmacology , Benzopyrans/pharmacokinetics , Butyrates/pharmacology , Butyrates/pharmacokinetics , Heterografts , Neoplasm Transplantation , Phytotherapy , Prostatic Neoplasms/pathology , Pyranocoumarins/metabolism , Animals , Benzopyrans/therapeutic use , Butyrates/therapeutic use , Cell Line , Disease Models, Animal , Dose-Response Relationship, Drug , Humans , Male , Mice, SCID , Mice, Transgenic , Plant Roots/chemistry , Prostatic Neoplasms/drug therapy , Pyranocoumarins/isolation & purification
7.
BMC Plant Biol ; 16(1): 177, 2016 08 15.
Article in English | MEDLINE | ID: mdl-27527830

ABSTRACT

BACKGROUND: Calophyllum brasiliense is highlighted as an important resource of calanolides, which are dipyranocoumarins that inhibit the reverse transcriptase of human immunodeficiency virus type 1 (HIV-1 RT). Despite having great medicinal importance, enzymes involved in calanolide, biosynthesis and the pathway itself, are still largely unknown. Additionally, no genomic resources exist for this plant species. RESULTS: In this work, we first analyzed the transcriptome of C. brasiliense leaves, stem, and roots using a RNA-seq strategy, which provided a dataset for functional gene mining. According to the structures of the calanolides, putative biosynthetic pathways were proposed. Finally, candidate unigenes in the transcriptome dataset, potentially involved in umbelliferone and calanolide (angular pyranocoumarin) biosynthetic pathways, were screened using mainly homology-based BLAST and phylogenetic analyses. CONCLUSIONS: The unigene dataset that was generated in this study provides an important resource for further molecular studies of C. brasiliense, especially for functional analysis of candidate genes involved in the biosynthetic pathways of linear and angular pyranocoumarins.


Subject(s)
Calophyllum/genetics , Plant Proteins/genetics , Pyranocoumarins/metabolism , Calophyllum/classification , Calophyllum/metabolism , Gene Expression Profiling , Phylogeny , Plant Proteins/metabolism , Transcriptome
8.
Am J Chin Med ; 44(2): 321-53, 2016.
Article in English | MEDLINE | ID: mdl-27080944

ABSTRACT

Herbal products containing Korean Angelica gigas Nakai (AGN) root extract are marketed as dietary supplements for memory enhancement, pain killing, and female menopausal symptom relief. We have shown the anticancer activities of AGN supplements in mouse models. To facilitate human anticancer translational research, we characterized the tissue distribution of AGN marker pyranocoumarin compounds decursin (D) and decursinol angelate (DA) ([Formula: see text]% in AGN) and their metabolite decursinol (DOH), assessed the safety of sub-chronic AGN dietary exposure in mice, and explored its impact on plasma aqueous metabolites and the prostate transcriptome. The data show that after a gavage dose, plasma contained readily detectable DOH, but little D and DA, mirroring patterns in the liver. Extra-hepatic tissues retained greater levels of DA and D than the liver did. For sub-chronic exposures, male mice were provided ad libitum AIN93M-pellet diets with 0.5 and 1% AGN for six weeks. No adverse effects were observed on the plasma biochemistry markers of liver and kidney integrity in spite of their enlargement. Histopathological examinations of the liver, kidney and other visceral organs did not reveal tissue abnormalities. Metabolomic assessment of plasma from mice fed the 1%-AGN diet suggested metabolic shifts of key amino acids especially in the methionine-cysteine cycle, purine cycle, and glycolysis-citrate cycle. Prostate transcriptomic profiling identified gene signature changes in the metabolisms of drugs, lipids and cellular energetics, neuro-muscular features, immunity and inflammation, and tumor suppressor/oncogene balance. The safety profile was corroborated with a daily [Formula: see text] injection of AGN extract (100-300[Formula: see text]mg/kg) for four weeks, which resulted in much greater systemic pyranocoumarin exposure than the dietary route did.


Subject(s)
Angelica/chemistry , Antineoplastic Agents, Phytogenic , Dietary Supplements , Metabolome , Plant Extracts/pharmacology , Prostate/metabolism , Pyranocoumarins/metabolism , Transcriptome , Animals , Benzopyrans/metabolism , Butyrates/metabolism , Female , Injections, Intraperitoneal , Male , Mice, Inbred C57BL , Plant Extracts/administration & dosage , Plant Extracts/isolation & purification , Plant Roots/chemistry , Tissue Distribution
9.
Drug Metab Pharmacokinet ; 30(1): 89-96, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25760535

ABSTRACT

F18 (10-chloromethyl-11-demethyl-12-oxo-calanolide), an analog of (+)-Calanolide A, is a novel small-molecule nonnucleoside reverse transcriptase inhibitor for the therapy of human immunodeficiency virus (HIV) infection. M3, the most abundant primary metabolite of F18 in human liver microsomes (HLMs) and rat liver microsomes (RLMs), is mainly excreted in bile as a glucuronide conjugate in rats after oral administration. The aim of this study was to identify the UDP glucuronosyltransferase (UGT) isoforms involved in the glucuronidation of M3 by HLMs and recombinant human UGTs and investigate the metabolic interactions of M3 with the substrates of UGTs in HLMs. As a result, UGT1A1 was the major isozyme responsible for the glucuronidation of M3, followed by UGT1A4, UGT1A9 and UGT2B7. M3 exhibited significant inhibition against UGT1A9 and UGT2B7 in both HLMs and recombinant human UGTs. In addition, M3 inhibited UGT1A9 catalyzed mycophenolic acid (MPA) glucuronidation with Ki of 0.39 µM, and M3 also inhibited the glucuronidation of 3'-azido-3'-deoxythymidine (AZT) by a "mixed-type" mechanism with Ki of 16.8 µM. The results suggest that UGT1A1 provides the major contribution to M3 glucuronidation in vitro and M3 has the potential to interact with xenobiotics and endogenous chemicals that are UGT1A9 and UGT 2B7 substrates.


Subject(s)
Glucuronides/metabolism , Glucuronosyltransferase/metabolism , Microsomes, Liver/metabolism , Pyranocoumarins/metabolism , Xenobiotics/metabolism , Chromatography, High Pressure Liquid , Drug Interactions , Glucuronosyltransferase/genetics , Humans , In Vitro Techniques , Isoenzymes , Microsomes, Liver/enzymology , Recombinant Proteins , Substrate Specificity , Tandem Mass Spectrometry
10.
Appl Biochem Biotechnol ; 175(2): 1168-80, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25374140

ABSTRACT

Binding of phenyl derivative of pyranocoumarin (PDP) modulated activity of fungal endopolygalacturonase in silico. Induced fit docking study of PDP with endopolygalacturonase (1HG8) showed a bifurcated hydrogen bond interaction with the protein at Lys 244 with a docking score of -3.6 and glide energy of -37.30 kcal/mol. Docking with endopolygalacturonase II (1CZF) resulted hydrogen bond formation with Lys 258 with a docking score of -2.3 and glide energy of -30.42 kcal/mol. It was hypothesized that this modulation favors accumulation of cell wall fragments (oligogalacturonides) which act as elicitors of plant defense responses. In order to prove the same, in vivo studies were carried out using a formulation developed from PDP (PDP 5EC) on greenhouse grown Lycopersicon esculentum L. The formulation was effective at different concentrations in reduction of seed infection, improvement of vigor and control of Fusarium oxysporum f.sp. lycopersici infection in L. esculentum. At a concentration of 2 %, PDP 5EC significant reduction in seed infection (95.83 %), improvement in seed vigor (64.31 %) and control of F. oxysporum f.sp. lycopersici infection (96.15 %) were observed. Further application of PDP 5EC to L. esculentum challenged with F. oxysporum f.sp. lycopersici significantly increased the activity of enzymes of the phenylpropanoid pathway, namely, peroxidase (PO), polyphenol oxidase (PPO), phenylalanine ammonia lyase (PAL), and enhanced the total phenolic content when compared to the control.


Subject(s)
Fusarium/physiology , Plant Diseases/microbiology , Plant Diseases/prevention & control , Polygalacturonase/biosynthesis , Propanols/metabolism , Pyranocoumarins/pharmacology , Solanum lycopersicum/drug effects , Alkanes/chemistry , Enzyme Induction/drug effects , Germination , Solanum lycopersicum/enzymology , Solanum lycopersicum/metabolism , Solanum lycopersicum/microbiology , Models, Molecular , Molecular Docking Simulation , Polygalacturonase/chemistry , Polygalacturonase/metabolism , Protein Conformation , Pyranocoumarins/chemistry , Pyranocoumarins/metabolism , Seeds/growth & development , Seeds/microbiology
11.
Phytochemistry ; 95: 197-206, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23993295

ABSTRACT

The medicinal plant Ammi visnaga is a valuable source of furanochromones and pyranocoumarins used as vasodilator agents. Its ability to germinate under unfavourable growth conditions, such as saline soil and hypoxia characterizing clay soils and marshes ecosystems, prompted us to qualitatively characterize secondary metabolites in umbels of A. visnaga plants grown under different conditions (in field, hydroponically controlled, and contrasted by salinity and/or hypoxia) by HPLC-ESI/IT/MS(n) analysis. Subsequently, the quantitative analysis of the bioactive compounds, above all furanochromones and pyranocoumarins, was carried out by HPLC-ESI/QqQ/MS/MS. The results show the influence of growing conditions on the quali-quantitative profile of A. visnaga secondary metabolites and evidence that hydroponic culture leads to increased level of A. visnaga active principles. Furthermore, two furanochromones never reported before were identified and characterized by 1D- and 2D-NMR analysis.


Subject(s)
Ammi/metabolism , Chromones/metabolism , Environment , Inflorescence/metabolism , Plant Extracts , Pyranocoumarins/metabolism , Stress, Physiological , Ammi/chemistry , Ammi/growth & development , Chromones/isolation & purification , Furans/metabolism , Hydroponics , Inflorescence/chemistry , Oxygen/metabolism , Plant Extracts/analysis , Salinity , Sodium Chloride/metabolism
12.
Planta Med ; 79(16): 1536-44, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24026903

ABSTRACT

The aim of this study is to investigate and compare the metabolic rate and profiles of pyranocoumarin isomers decursin and decursinol angelate using liver microsomes from humans and rodents, and to characterize the major metabolites of decursin and decursinol angelate in human liver microsomal incubations using LC-MS/MS. First, we conducted liver microsomal incubations of decursin and decursinol angelate in the presence or absence of NADPH. We found that in the absence of NADPH, decursin was efficiently hydrolyzed to decursinol by hepatic esterase(s), but decursinol angelate was not. In contrast, formation of decursinol from decursinol angelate was mediated mainly by cytochrome P450(s). Second, we measured the metabolic rate of decursin and decursinol angelate in liver S9 fractions from mice and humans. We found that human liver S9 fractions metabolized both decursin and decursinol angelate more slowly than those of the mouse. Third, we characterized the major metabolites of decursin and decursinol angelate from human liver microsomes incubations using HPLC-UV and LC-MS/MS methods and assessed the in vivo metabolites in mouse plasma from a one-dose PK study. Decursin and decursinol angelate have different metabolite profiles. Nine metabolites of decursin and nine metabolites of decursinol angelate were identified in human liver microsome incubations besides decursinol using a hybrid triple quadruple linear ion trap LC-MS/MS system, and many of them were later verified to be also present in plasma samples from rodent PK studies.


Subject(s)
Benzopyrans/metabolism , Butyrates/metabolism , Microsomes, Liver/metabolism , Pyranocoumarins/metabolism , Animals , Apiaceae/chemistry , Benzopyrans/isolation & purification , Butyrates/isolation & purification , Chromatography, High Pressure Liquid , Female , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Inbred Strains , Pyranocoumarins/isolation & purification , Rats , Rats, Sprague-Dawley
13.
J Biomed Biotechnol ; 2012: 310850, 2012.
Article in English | MEDLINE | ID: mdl-22778547

ABSTRACT

Antifungal activity of petroleum ether extract of Psoralea corylifolia L. seed, tested against Fusarium sp. namely, Fusarium oxysporum, Fusarium moniliforme, and Fusarium graminearum, was evaluated by agar well diffusion assay. The chromatographic fractionation of the extract yielded a new phenyl derivative of pyranocoumarin (PDP). The structure of the PDP was confirmed using spectroscopic characterization (GC-MS, IR, and NMR), and a molecular mass of m/z 414 [M-2H](+) with molecular formula C(27)H(28)O(4) was obtained. The PDP had a potent antifungal activity with a minimum inhibitory concentration of 1 mg/mL against Fusarium sp. Molecular docking using Grid-Based Ligand Docking with Energetics (GLIDE, Schrodinger) was carried out with the Tri101, trichothecene 3-O-acetyltransferase, as target protein to propose a mechanism for the antifungal activity. The ligand PDP showed bifurcated hydrogen bond interaction with active site residues at TYR 413 and a single hydrogen bond interaction at ARG 402 with a docking score -7.19 and glide energy of -45.78 kcal/mol. This indicated a strong binding of the ligand with the trichothecene 3-O-acetyltransferase, preventing as a result the acetylation of the trichothecene mycotoxin and destruction of the "self-defense mechanism" of the Fusarium sp.


Subject(s)
Acetyltransferases/antagonists & inhibitors , Antifungal Agents/pharmacology , Plant Diseases/prevention & control , Psoralea/chemistry , Pyranocoumarins/pharmacology , Acetylation/drug effects , Acetyltransferases/chemistry , Acetyltransferases/metabolism , Alkanes , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Antifungal Agents/metabolism , Chemical Fractionation , Fusarium/drug effects , Fusarium/enzymology , Microbial Sensitivity Tests , Models, Molecular , Plant Extracts/chemistry , Protein Binding , Pyranocoumarins/chemistry , Pyranocoumarins/isolation & purification , Pyranocoumarins/metabolism , Seeds/chemistry , Spectrum Analysis , Thermodynamics
14.
J Nat Prod ; 73(8): 1394-7, 2010 Aug 27.
Article in English | MEDLINE | ID: mdl-20701298

ABSTRACT

Phenylalanine ammonia-lyase (PAL) and cinnamate 4-hydroxylase (C4H) are important enzymes in the phenylpropanoid pathway and also in the accumulation of decursin (1) and decursinol angelate (2), which are major secondary metabolites in Angelica gigas. Using PCR with degenerate primers targeted to conserved regions of available orthologous PAL and C4H sequences, cDNAs encoding PAL and C4H from A. gigas were isolated. Both genes were used to show the comparative developmental and inducible accumulation of mRNAs in different organs and in suspension cells of A. gigas. PAL and C4H were induced most strongly in response to 300 microM methyl jasmonate treatment at 6 and 12 h, respectively, and were highly expressed in the fine roots of A. gigas. Similarly, the production of 1 and 2 was most prolific in the fine roots of the plant.


Subject(s)
Angelica , Phenylalanine Ammonia-Lyase/genetics , Phenylalanine Ammonia-Lyase/metabolism , Phenylpropionates/metabolism , Pyranocoumarins/metabolism , Trans-Cinnamate 4-Monooxygenase/genetics , Trans-Cinnamate 4-Monooxygenase/metabolism , Angelica/enzymology , Angelica/genetics , Benzopyrans/analysis , Benzopyrans/chemistry , Butyrates/analysis , Butyrates/chemistry , Chromatography, High Pressure Liquid , Gene Expression Regulation, Plant , Molecular Structure , Plant Roots/enzymology , Plant Roots/genetics , Pyranocoumarins/chemistry , RNA, Messenger/analysis
15.
Bioorg Med Chem Lett ; 19(22): 6447-51, 2009 Nov 15.
Article in English | MEDLINE | ID: mdl-19811915

ABSTRACT

A series of pyranocoumarin derivatives were synthesized and evaluated in vivo for their anti-hyperglycemic as well as anti-dyslipidemic activities. Compounds 7a, 7c, 8a, 8b, 8c, 8e and 8f have shown promising anti-hyperglycemic activities in sucrose loaded model (SLM) as well as sucrose challenged streptozotocin induced diabetic rat model (STZ). Compounds 8a and 8b were showing 38.0% and 42.0% blood glucose lowering activity in db/db mice model. In vitro anti-hyperglycemic activity evaluation exhibited that compounds 8a (IC(50)=24.5 microM) and 8b (IC(50)=36.2 microM) are potential PTP-1B inhibitors thereby revealing their possible mechanism of anti-diabetic action. Compounds 7a, 7b, 8a, 8b, 8d, 8e and 8f have shown significant anti-dyslipidemic activity in triton induced dyslipidemia in rats.


Subject(s)
Blood Glucose , Diabetes Mellitus, Experimental/drug therapy , Dyslipidemias/drug therapy , Pyranocoumarins/therapeutic use , Animals , Diabetes Mellitus, Experimental/blood , Dyslipidemias/blood , Hypoglycemic Agents/classification , Hypoglycemic Agents/therapeutic use , Lipid Metabolism/drug effects , Mice , Mice, Inbred C57BL , PPAR gamma/metabolism , Pyranocoumarins/metabolism , Rats , Rats, Wistar , Structure-Activity Relationship
16.
J Biotechnol ; 130(4): 346-53, 2007 Jul 15.
Article in English | MEDLINE | ID: mdl-17601621

ABSTRACT

Callus cultures of Calophyllum inophyllum were established using seed, nodal/ internodal and leaf explants on WPM basal medium supplemented with indole-3-butyric acid (IBA), alpha-naphthalene acetic acid (NAA), picloram (4-amino-3,5,6-trichloropicolinic acid), and 6-benzylaminopurine (BAP) in different combinations and concentrations with the view to study the influence of hormones on callus induction and the pattern of expression of dipyranocoumarins including anti-HIV, non-nucleoside reverse transcriptase inhibitors inophyllum B and P in callus cultures. 96.01% seed explants, 87.50% nodal/internodal explants and 86.66% leaf explants were converted into calluses when inoculated on WPM supplemented with IBA 4.0 mg l(-1) along with BAP 1.0 mg l(-1), IBA 4.0 mg l(-1), and picloram 6.0 mg l(-1) along with BAP 2.0 mg l(-1), respectively. Calluses induced from seed explants were white, friable and irregular whereas nodal/internodal and leaf explants induced dark brown, nodular and compact calluses. In order to facilitate the rapid quantitative analysis of dipyranocoumarins under study, a novel HPLC method capable of separating all six dipyranocoumarins in a single isocratic run has been optimized. Quantitative HPLC analysis of callus extracts revealed that highest inophyllum B (40.59 mg 100g callus(-1)) was expressed in callus induced from seed explant on medium containing 2.0 mg l(-1) indole-3-butyric acid, while highest inophyllum P (141.35 mg 100g callus(-1)) was estimated in seed callus induced on medium containing 2.0 mg l(-1) indole-3-butyric acid along with BAP 1.0 mg l(-1).


Subject(s)
Anti-HIV Agents/metabolism , Calophyllum/metabolism , Cell Culture Techniques/methods , Gene Expression Regulation, Plant/physiology , Plant Growth Regulators/pharmacology , Pyranocoumarins/metabolism , Seeds/metabolism , Calophyllum/drug effects , Calophyllum/growth & development , Cells, Cultured , Gene Expression Regulation, Plant/drug effects , Seeds/drug effects
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