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.

scholarly journals Bioconversion of Corticosterone into Corticosterone-Glucoside by Glucosyltransferase

Molecules ◽  
2018 ◽  
Vol 23 (7) ◽  
pp. 1783 ◽  
Author(s):  
Tokutaro Yamaguchi ◽  
Joo-Ho Lee ◽  
A-Rang Lim ◽  
Joon-Soo Sim ◽  
Eun-Ji Yu ◽  
...  
Keyword(s):  
High Resolution Mass Spectrometry ◽  
Hydroxyl Group ◽  
Oxygen Species ◽  
Neuroprotective Agents ◽  
Neuroprotective Effects ◽  
The Difference ◽  
First Time ◽  
Resolution Mass

Glucosylation of the 21-hydroxyl group of glucocorticoid changes its solubility into hydrophilicity from hydrophobicity and, as with glucocorticoid glucuronides as a moving object in vivo, it is conceivable that it exhibits the same behavior. Therefore, glucosylation to the 21-hydroxyl group while maintaining the 11β-hydroxyl group is particularly important, and glucosylation of corticosterone was confirmed by high-resolution mass spectrometry and 1D (1H and 13C) and 2D (COSY, ROESY, HSQC-DEPT and HMBC) NMR. Moreover, the difference in bioactivity between corticosterone and corticosterone 21-glucoside was investigated in vitro. Corticosterone 21-glucoside showed greater neuroprotective effects against H2O2-induced cell death and reactive oxygen species (ROS) compared with corticosterone. These results for the first time demonstrate that bioconversion of corticosterone through the region-selective glucosylation of a novel compound can present structural potential for developing new neuroprotective agents.

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 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.

scholarly journals Human Hepatocyte Metabolism of Novel Synthetic Cannabinoids MN-18 and Its 5-Fluoro Analog 5F-MN-18

2017 ◽  
Vol 63 (11) ◽  
pp. 1753-1763 ◽  
Author(s):  
Xingxing Diao ◽  
Jeremy Carlier ◽  
Mingshe Zhu ◽  
Marilyn A Huestis
Keyword(s):  
Carboxylic Acid ◽  
High Resolution ◽  
High Resolution Mass Spectrometry ◽  
Synthetic Cannabinoids ◽  
Human Hepatocytes ◽  
Binding Affinities ◽  
High Resolution Mass ◽  
Full Scan ◽  
Resolution Mass

Abstract BACKGROUND In 2014, 2 novel synthetic cannabinoids, MN-18 and its 5-fluoro analog, 5F-MN-18, were first identified in an ongoing survey of novel psychoactive substances in Japan. In vitro pharmacological assays revealed that MN-18 and 5F-MN-18 displayed high binding affinities to human CB1 and CB2 receptors, with Ki being 1.65–3.86 nmol/L. MN-18 and 5F-MN-18 were scheduled in Japan and some other countries in 2014. Despite increasing prevalence, no human metabolism data are currently available, making it challenging for forensic laboratories to confirm intake of MN-18 or 5F-MN-18. METHODS We incubated 10 μmol/L of MN-18 and 5F-MN-18 in human hepatocytes for 3 h and analyzed the samples on a TripleTOF 5600+ high-resolution mass spectrometer to identify appropriate marker metabolites. Data were acquired via full scan and information-dependent acquisition-triggered product ion scans with mass defect filter. RESULTS In total, 13 MN-18 metabolites were detected, with the top 3 abundant metabolites being 1-pentyl-1H-indazole-3-carboxylic acid, pentyl-carbonylated MN-18, and naphthalene-hydroxylated MN-18. For 5F-MN-18, 20 metabolites were observed, with the top 3 abundant metabolites being 5′-OH-MN-18, MN-18 pentanoic acid, and 1-(5-fluoropentyl)-1H-indazole-3-carboxylic acid. CONCLUSIONS We have characterized MN-18 and 5F-MN-18 metabolism with human hepatocytes and high-resolution mass spectrometry, and we recommend characteristic major metabolites for clinical and forensic laboratories to identify MN-18 and 5F-MN-18 intake and link observed adverse events to these novel synthetic cannabinoids.

Cytotoxic Activity of tropane alkaloides of Species of Erythroxylum

2021 ◽  
Vol 21 ◽  
Author(s):  
José Fernando Araújo Neto ◽  
Erika Maria de Oliveira Ribeiro ◽  
Ademir Evangelista do Vale ◽  
Jorge Maurício David ◽  
Juceni Pereira de Lima David
Keyword(s):  
Natural Products ◽  
Cytotoxic Activity ◽  
Screening Program ◽  
Evaluation Studies ◽  
Tropane Alkaloids ◽  
Chemotherapeutic Agents ◽  
In Vitro Tests ◽  
Cytotoxic Activities ◽  
Cytotoxic Potential

: Erythroxylaceae is a family composed of four genera being Erythroxylum the only one represented in the Neotropical region. Chemical studies indicate the presence of alkaloids, terpenes, flavonoids and phenolic compounds as main compounds. The incorporation of cytotoxic activity assays of natural products using cell cultures assists in the selection of potential chemotherapeutic agents. In this work we describe a revision of the cytotoxicity evaluation studies performed with extracts and/or pure substances obtained from Erythroxylum species through an integrative review. We have found studies that evaluated the cytotoxic activity of 21 species of Erythroxylum against 45 different cell lines, the analysis of the chemical composition of these species shows that the metabolites present in each species influence the cytotoxic potential of them, especially the presence of disubstituted tropane alkaloids species with the highest cytotoxic potential. MTT and Sulforrodamine B assays were the main in vitro tests used for the evaluation of the cytotoxic activities. From the total of species, less than 10% of the Erythroxylum species have already been evaluated for the cytotoxic activity, four of them showed high cytotoxic activity according to with the criteria of the NCI plant screening program. Thus, this genus represents a potential source of natural products with antitumor activity.

In vitro and in vivo metabolism of 3-quinuclidinyl benzilate by high-resolution mass spectrometry

2020 ◽  
Vol 190 ◽  
pp. 113519
Author(s):  
Martin Uher ◽  
Martin Mžik ◽  
Jana Žďárová Karasová ◽  
David Herman ◽  
Lenka Čechová ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
High Resolution Mass Spectrometry ◽  
In Vivo Metabolism ◽  
High Resolution Mass ◽  
Resolution Mass ◽  
Quinuclidinyl Benzilate
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