scholarly journals Targeted Isolation of a Cytotoxic Cyclic Hexadepsipeptide from the Mesophotic Zone Sponge-Associated Fungus Cymostachys sp. NBUF082

Marine Drugs ◽  
2021 ◽  
Vol 19 (10) ◽  
pp. 565
Author(s):  
Ye Yuan ◽  
Te Li ◽  
Tingting Wang ◽  
C. Benjamin Naman ◽  
Jing Ye ◽  
...  
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
High Resolution Mass Spectrometry ◽  
2D Nmr ◽  
Lymphocytic Leukemia ◽  
Leukemia Cells ◽  
Chiral Hplc ◽  
2D Nmr Spectroscopy ◽  
Ic50 Value ◽  
Resolution Mass

LC-MS/MS-based molecular networking facilitated the targeted isolation of a new cyclic hexadepsipeptide, cymodepsipeptide (1), and two known analogues, RF–2691A (2) and RF–2691B (3), from the fungus Cymostachys sp. NBUF082 that was derived from a mesophotic zone Aaptos sponge collected near Apo Island. The constitution and configuration of 1 was elucidated through 1D and 2D NMR-spectroscopy, high resolution mass-spectrometry, and chemical degradations including Marfey’s analysis and chiral HPLC. It was observed that 1 was moderately cytotoxic against CCRF-CEM human acute lymphocytic leukemia cells in vitro with the IC50 value of 9.2 ± 1.1 μM.

scholarly journals A New Glucuronolactone Glycoside Phoenixoside B from the Seeds of Phoenix Dactylifera

2013 ◽  
Vol 8 (9) ◽  
pp. 1934578X1300800
Author(s):  
Sumbul Azmat ◽  
Rehana Ifzal ◽  
Faryal Vali Mohammad ◽  
Viqar Uddin Ahmad ◽  
Aqib Zahoor
Keyword(s):  
Mass Spectrometry ◽  
Nmr Spectroscopy ◽  
High Resolution ◽  
High Resolution Mass Spectrometry ◽  
Soluble Fraction ◽  
2D Nmr ◽  
Phoenix Dactylifera ◽  
2D Nmr Spectroscopy ◽  
High Resolution Mass ◽  
Resolution Mass

A new glucuronolactone glycoside, phoenixoside B (1), has been isolated from the n-butanol soluble fraction of seeds of Phoenix dactylifera. The structure was characterized as 1-(1-ethyl-β-D-glucosyl)-4,5-diethyl-[α-D-glucofuranourono-6,3-lactone] on the basis of 1D and 2D-NMR spectroscopy and high-resolution mass spectrometry.

scholarly journals The Difference in Cytotoxic Activity between Two Optical Isomers of Gelsemine from Gelsemium elegans Benth. on PC12 Cells

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 2004
Author(s):  
Li Lin ◽  
Yan-Chun Liu ◽  
Zhao-Ying Liu
Keyword(s):  
Cytotoxic Activity ◽  
Pc12 Cells ◽  
High Resolution Mass Spectrometry ◽  
Optical Isomers ◽  
Cytotoxic Potential ◽  
Whole Plant ◽  
Ic50 Value ◽  
The Difference ◽  
Resolution Mass

Two optical isomers, +/− gelsemine (1, 2), together with one known compound were isolated from the whole plant of G. elegans. The structures of the separated constituents were elucidated on 1D and 2D (1H-1H COSY, HMBC, HSQC) NMR spectroscopy and high-resolution mass spectrometry (HRMS). The isolated alkaloids were tested in vitro for cytotoxic potential against PC12 cells by the MTT assay. As a result, (+) gelsemine (compound 1) exhibited cytotoxic activity against PC12 cells with an IC50 value of 31.59 μM, while (−) gelsemine (compound 2) was not cytotoxic.

A New Sesquiterpene Lactone Sulfate from Reichardia gaditana (Asteraceae)

2007 ◽  
Vol 62 (1) ◽  
pp. 132-134 ◽  
Author(s):  
Christian Zidorn ◽  
Ernst-Peter Ellmerer ◽  
Werner Heller ◽  
Richard Greil ◽  
Manuela Guggenberger ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Nmr Spectroscopy ◽  
High Resolution ◽  
Structure Elucidation ◽  
Methanolic Extract ◽  
High Resolution Mass Spectrometry ◽  
2D Nmr ◽  
2D Nmr Spectroscopy ◽  
Asteraceae Family ◽  
Resolution Mass

The new sesquiterpenoid 8-deoxy-15-(3′-hydroxy-2′-methyl-propanoyl)-lactucin 3′-sulfate (1) was isolated from the methanolic extract of roots of Reichardia gaditana L. The compound was isolated by silica gel column chromatography (CC) and repeated Sephadex LH-20 CC. Structure elucidation was accomplished by high-resolution mass spectrometry and by 1D- and 2D-NMR spectroscopy. The chemosystematic significance of the new compound is discussed in the context of sesquiterpenoids from other members of the Lactuceae tribe of the Asteraceae family.

scholarly journals A New Megastigmane Glycoside, Phoenixoside A, from Phoenix Dactylifera

2012 ◽  
Vol 7 (1) ◽  
pp. 1934578X1200700
Author(s):  
Sumbul Azmat ◽  
Aqib Zahoor ◽  
Rehana Ifzal ◽  
Viqar Uddin Ahmad ◽  
Faryal Vali Mohammed
Keyword(s):  
Mass Spectrometry ◽  
Nmr Spectroscopy ◽  
High Resolution ◽  
High Resolution Mass Spectrometry ◽  
Soluble Fraction ◽  
2D Nmr ◽  
Phoenix Dactylifera ◽  
Cd Spectroscopy ◽  
2D Nmr Spectroscopy ◽  
Resolution Mass

A new megastigmane glycoside, phoenixoside A (1), has been isolated from the n-butanol - soluble fraction of seeds of Phoenix dactylifera. The structure was characterized as (6S,7Z,9R)-hydroxy-3-oxo-ionol-9- O-β-D-glucopyranosyl-(1″→6′)-β-D–glucopyranoside on the basis of 1D and 2D NMR spectroscopy, high-resolution mass spectrometry, and CD spectroscopy.

Toll-Like Receptor 7-Targeting of Human B-Lineage Acute Lymphocytic Leukemia Induces Immunogeneicity and Apoptosis of Leukemia Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 706-706 ◽  
Author(s):  
Xueqing Liang ◽  
Jakub Tolar ◽  
Jeffery S. Miller ◽  
Tucker W. LeBien ◽  
Bruce R. Blazar ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Acute Lymphocytic Leukemia ◽  
Scid Mice ◽  
Lymphocytic Leukemia ◽  
Leukemia Cells ◽  
Tlr7 Agonist ◽  
B Lineage

Abstract Acute lymphocytic leukemia (ALL) is the most common childhood leukemia and remains a difficult disease with poor survival in patients who have failed standard therapy. New therapeutic strategies are needed to achieve longer survival and improved cure rates in both pediatric and adult ALL patients. In this study, we show human B-lineage acute lymphocytic leukemia (B-ALL) cell lines (6/6 tested) and CD19+CD10+ primary B-ALL cells from patients (8/8 tested) express TLR7 mRNA by real-time RT-PCR and TLR7 proteins by Western blot. Triggering TLR7 on B-ALL cells with a TLR7 agonist (imiquimod) significantly increases the cell surface expression of molecules essential for T cell activation (CD40, CD54, CD80, CD86, and HLA-DR), the ligands for NKG2D and ligands for natural cytotoxicity receptors (NKp30, NKp44, and NKp46) which regulate NK-mediate killing. Thus, TLR7 signaling enhances the immunogenicity of B-ALL cells and makes them more suitable targets for T cell and NK cell mediated attack. Most importantly, TLR7 agonists strongly suppress in vitro growth of B-ALL cell lines (RS4;11, BLIN-1) and induces profound apoptosis of primary B-ALL cells from patients in culture in a TLR7 agonist dose-dependent manner. Both t(4;11)-positive RS4;11 cells and t(4;11)-negative BLIN-1 cells proliferate rapidly in culture with a 30–40 fold increases of leukemia cell number in 7 days. The addition of TLR7 agonist at 10 ug/ml fully inhibit the growth of RS4;11 and BLIN-1 cells in culture. Furthermore, TLR7 agonist treatment dramatically induces apoptosis of primary B-ALL cells isolated from the patients (2/2 with t(9;22), 6/6 without t(9;22)) with 0.4%–13.3% leukemia cells left at day 5 of culture. The TLR7 agonist-mediated apoptotic death of B-ALL cells was conformed by viable cell counts, TMRE staining, and, Western blots of the activation and cleavage of caspases. To study the in vivo therapeutic effects of TLR7 agonist against human B-ALL, RS4;11 and BLIN-1 cells were luciferase labeled and injected into NOD/SCID mice. Both RS4;11 and BLIN-1 leukemia cells engrafted in multiple organs (BM, spleen, liver, lymph nodes, kidney) resulting in uniform lethality of RS4;11 mice in 8 weeks and BLIN-1 mice in 12 weeks, respectively. Flow cytometry and tissue staining results confirmed that these organs were massively infiltrated with human CD45+19+ leukemia cells. To determine whether TLR7 preincubation of RS4;11 or BLIN-1 cells would prolong survival due to an apoptotic effect, cohorts of mice were injected with a lethal dose of RS4;11 or BLIN-1 cells with or without pre-incubation with TLR7 agonist. Mice receiving TLR7 agonist pre-pretreated B-ALL cells had a significant increase in long-term survival rate and significant reduction in tumor burden at the time points evaluated. These in vivo results confirm previous in vitro findings and suggest that TLR agonist-treated B-ALL cells are programmed to die. The antitumor efficacy of systemic administration of TLR7 agonist in NOD/SCID mice with established B-ALL is being investigated using these xenograft mouse models. These results form the basis for a clinical trial of systemic TLR7 agonist administration for treating patients with B-ALL. In summary, we have shown that TLR7 targeting increases B-ALL immunogenicity and directly induces B-ALL apoptosis, providing new insights into the biology and therapy of B-ALL.

Toll-like receptor 7 agonist induces apoptosis of human B-lineage acute lymphocytic leukemia cells in vitro and in vivo

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 3033-3033
Author(s):  
X. Liang ◽  
J. Tolar ◽  
J. S. Miller ◽  
T. W. LeBien ◽  
B. R. Blazar ◽  
...  
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Leukemia Cells ◽  
Toll Like Receptor ◽  
B Lineage

scholarly journals Chromane Derivatives from Underground Parts of Iris tenuifolia and Their In Vitro Antimicrobial, Cytotoxicity and Antiproliferative Evaluation

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6705
Author(s):  
Oldokh Otgon ◽  
Suvd Nadmid ◽  
Christian Paetz ◽  
Hans-Martin Dahse ◽  
Kerstin Voigt ◽  
...  
Keyword(s):  
Ethanol Extract ◽  
2D Nmr ◽  
Inhibitory Effect ◽  
Leukemia Cells ◽  
Diffusion Method ◽  
2D Nmr Spectroscopy ◽  
Phytochemical Investigation ◽  
Potent Inhibitory Effect ◽  
New Compounds

Phytochemical investigation of the ethanol extract of underground parts of Iris tenuifolia Pall. afforded five new compounds; an unusual macrolide termed moniristenulide (1), 5-methoxy-6,7-methylenedioxy-4-O-2′-cycloflavan (2), 5,7,2′,3′-tetrahydroxyflavanone (3), 5-hydroxy-6,7-dimethoxyisoflavone-2′-O-β-d-glucopyranoside (9), 5,2′,3′-dihydroxy-6,7-dimethoxyisoflavone (10), along with seven known compounds (4–8, 11–12). The structures of all purified compounds were established by analysis of 1D and 2D NMR spectroscopy and HR-ESI-MS. The antimicrobial activity of the compounds 1–3, 5, 9, and 10 was investigated using the agar diffusion method against fungi, Gram-positive and Gram-negative bacteria. In consequence, new compound 3 was found to possess the highest antibacterial activity against Enterococcus faecalis VRE and Mycobacterium vaccae. Cell proliferation and cytotoxicity tests were also applied on all isolated compounds and plant crude extract in vitro with the result of potent inhibitory effect against leukemia cells. In particular, the newly discovered isoflavone 10 was active against both of the leukemia cells K-562 and THP-1 while 4–6 of the flavanone type compounds were active against only THP-1.

scholarly journals Amycolatomycins A and B, Cyclic Hexapeptides Isolated from an Amycolatopsis sp. 195334CR

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 261
Author(s):  
Gian Primahana ◽  
Chandra Risdian ◽  
Tjandrawati Mozef ◽  
Joachim Wink ◽  
Frank Surup ◽  
...  
Keyword(s):  
Inhibitory Concentration ◽  
High Resolution Mass Spectrometry ◽  
2D Nmr ◽  
2D Nmr Spectroscopy ◽  
Planar Structures ◽  
Cyclic Hexapeptides ◽  
Weak Activity ◽  
Absolute Stereochemistry ◽  
Resolution Mass ◽  
Acid Unit

The rare actinobacterium Amycolatopsis sp. strain 195334CR was found to produce previously undescribed cyclic hexapeptides, which we named amycolatomycin A and B (1 and 2). Their planar structures were determined by high-resolution mass spectrometry as well as extensive 1D and 2D NMR spectroscopy, while the absolute stereochemistry of its amino acids were determined by Marfey’s method. Moreover, 1 and 2 differ by the incorporation of l-Ile and l-allo-Ile, respectively, whose FDVA (Nα-(2,4-Dinitro-5-fluorphenyl)-L-valinamide) derivatives were separated on a C4 column. Their hallmark in common is a unique 2,6-dichloro-tryptophan amino acid unit. Amycolatomycin A (1) exhibited weak activity against Bacillus subtilis DSM 10 (minimum inhibitory concentration (MIC) = 33.4 µg/mL).

scholarly journals Nontargeted Metabolomics by High-Resolution Mass Spectrometry to Study the In Vitro Metabolism of a Dual Inverse Agonist of Estrogen-Related Receptors β and γ, DN203368

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 776
Author(s):  
Sin-Eun Kim ◽  
Seung-Bae Ji ◽  
Euihyeon Kim ◽  
Minseon Jeong ◽  
Jina Kim ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Human Liver ◽  
High Resolution Mass Spectrometry ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Rat Liver Microsomes ◽  
High Resolution Mass ◽  
Resolution Mass

DN203368 ((E)-3-[1-(4-[4-isopropylpiperazine-1-yl]phenyl) 3-methyl-2-phenylbut-1-en-1-yl] phenol) is a 4-hydroxy tamoxifen analog that is a dual inverse agonist of estrogen-related receptor β/γ (ERRβ/γ). ERRγ is an orphan nuclear receptor that plays an important role in development and homeostasis and holds potential as a novel therapeutic target in metabolic diseases such as diabetes mellitus, obesity, and cancer. ERRβ is also one of the orphan nuclear receptors critical for many biological processes, such as development. We investigated the in vitro metabolism of DN203368 by conventional and metabolomic approaches using high-resolution mass spectrometry. The compound (100 μM) was incubated with rat and human liver microsomes in the presence of NADPH. In the metabolomic approach, the m/z value and retention time information obtained from the sample and heat-inactivated control group were statistically evaluated using principal component analysis and orthogonal partial least-squares discriminant analysis. Significant features responsible for group separation were then identified using tandem mass spectra. Seven metabolites of DN203368 were identified in rat liver microsomes and the metabolic pathways include hydroxylation (M1-3), N-oxidation (M4), N-deisopropylation (M5), N,N-dealkylation (M6), and oxidation and dehydrogenation (M7). Only five metabolites (M2, M3, and M5-M7) were detected in human liver microsomes. In the conventional approach using extracted ion monitoring for values of mass increase or decrease by known metabolic reactions, only five metabolites (M1-M5) were found in rat liver microsomes, whereas three metabolites (M2, M3, and M5) were found in human liver microsomes. This study revealed that nontargeted metabolomics combined with high-resolution mass spectrometry and multivariate analysis could be a more efficient tool for drug metabolite identification than the conventional approach. These results might also be useful for understanding the pharmacokinetics and metabolism of DN203368 in animals and humans.

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