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Malva sylvestris L. extract suppresses desferrioxamine‐induced PGE2 and PGD2 release in differentiated U937 cells: the development and validation of an LC‐MS/MS method for prostaglandin quantification 下载免费PDF全文
Cleverson Antonio Ferreira Martins Almeriane Maria Weffort‐Santos João Cleverson Gasparetto Angela Cristina Leal Badaró Trindade Michel Fleith Otuki Roberto Pontarolo 《Biomedical chromatography : BMC》2014,28(7):986-993
Malva sylvestris is a species used worldwide as an alternative to anti‐inflammatory therapies; however, its mechanism of action remains unknown. In this paper, the anti‐inflammatory effects of M. sylvestris alcoholic extracts were evaluated by measuring the pro‐inflammatory mediators PGE2 and PGD2 in desferrioxamine‐stimulated phorbol 12‐myristate 13‐acetate‐differentiated U937 cells. An HPLC‐DAD fingerprint of the M. sylvestris extract was performed and caffeic acid, ferulic acid and scopoletin were identified and quantified. An HPLC‐MS/MS method was developed and validated to separate and measure the prostaglandins. The lower limits of detection (~0.5 ng/mL for PGE2 and PGD2) and quantification (1.0 ng/mL for PGE2 and PGD2) indicated that the method is highly sensitive. The calibration curves showed excellent coefficients of correlation (r > 0.99) over the range of 1.0–500.0 ng/mL, and at different levels, the accuracy ranged from 96.4 to 106.4% with an RSD < 10.0% for the precision study. This method was successfully applied using U937‐d cells. A significant dose‐dependent reduction of PGE2 and PGD2 levels occurred using 10 µg/mL (10.74 ± 2.86 and 9.60 ± 6.89%) and 50 µg/mL of extract (48.37 ± 3.24 and 53.06 ± 6.15%), suggesting that the anti‐inflammatory mechanisms evoked by M. sylvestris may be related to modulation of these mediators. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
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The structures of archaeal glycerophospholipids and glycolipids are unique in that they consist of phytanyl substituents ether linked to the glycerol backbone, imparting stability to the molecules. In this contribution, we described multiple-stage linear ion-trap combined with high resolution mass spectrometry toward structural characterization of this lipid family desorbed as lithiated adduct ions or as the [M−H]− and [M−2H]2− ions by ESI. MSn on various forms of the lithiated adduct ions yielded rich structurally informative ions leading to complete structure identification of this lipid family, including the location of the methyl branches of the phytanyl chain. By contrast, structural information deriving from MSn on the [M−H]− and [M−2H]2− ions is not complete. The fragmentation pathways in an ion-trap, including unusual internal loss of glycerol moiety and internal loss of hexose found for this lipid family were proposed. This mass spectrometric approach provides a simple tool to facilitate confident characterization of this unique lipid family. 相似文献
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Access to New Endoperoxide Derivatives by Electrochemical Oxidation of Substituted 3‐Azabicyclo[4.1.0]hept‐4‐enes 下载免费PDF全文
Dr. Frédérick Nuter Dr. Abdou Khadre Djily Dimé Dr. Cheng Chen Dr. Lotfi Bounaadja Dr. Elisabeth Mouray Dr. Isabelle Florent Dr. Yvan Six Dr. Olivier Buriez Dr. Angela Marinetti Dr. Arnaud Voituriez 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(14):5584-5593
A series of substituted 3‐azabicyclo[4.1.0]hept‐4‐ene derivatives were prepared and analysed by cyclic voltammetry. Preparative aerobic electrochemical oxidation reactions were then carried out. Three original endoperoxides were isolated, characterised and subjected to antimalarial and cytotoxicity activity assays. 相似文献
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Synthesis and Biological Evaluation of RGD Peptidomimetic–Paclitaxel Conjugates Bearing Lysosomally Cleavable Linkers 下载免费PDF全文
Alberto Dal Corso Dr. Michele Caruso Dr. Laura Belvisi Dr. Daniela Arosio Prof. Dr. Umberto Piarulli Dr. Clara Albanese Dr. Fabio Gasparri Dr. Aurelio Marsiglio Dr. Francesco Sola Dr. Sonia Troiani Dr. Barbara Valsasina Dr. Luca Pignataro Dr. Daniele Donati Prof. Dr. Cesare Gennari 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(18):6921-6929
Two small‐molecule–drug conjugates (SMDCs, 6 and 7 ) featuring lysosomally cleavable linkers (namely the Val–Ala and Phe–Lys peptide sequences) were synthesized by conjugation of the αvβ3‐integrin ligand cyclo[DKP–RGD]‐CH2NH2 ( 2 ) to the anticancer drug paclitaxel (PTX). A third cyclo[DKP–RGD]–PTX conjugate with a nonpeptide “uncleavable” linker ( 8 ) was also synthesized to be tested as a negative control. These three SMDCs were able to inhibit biotinylated vitronectin binding to the purified αVβ3‐integrin receptor at nanomolar concentrations and showed good stability at pH 7.4 and pH 5.5. Cleavage of the two peptide linkers was observed in the presence of lysosomal enzymes, whereas conjugate 8 , which possesses a nonpeptide “uncleavable” linker, remained intact under these conditions. The antiproliferative activities of the conjugates were evaluated against two isogenic cell lines expressing the integrin receptor at different levels: the acute lymphoblastic leukemia cell line CCRF‐CEM (αVβ3?) and its subclone CCRF‐CEM αVβ3 (αVβ3+). Fairly effective integrin targeting was displayed by the cyclo[DKP–RGD]–Val–Ala–PTX conjugate ( 6 ), which was found to differentially inhibit proliferation in antigen‐positive CCRF‐CEM αVβ3 versus antigen‐negative isogenic CCRF‐CEM cells. The total lack of activity displayed by the “uncleavable” cyclo[DKP–RGD]–PTX conjugate ( 8 ) clearly demonstrates the importance of the peptide linker for achieving the selective release of the cytotoxic payload. 相似文献
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Analysis of non‐derivatised bacteriohopanepolyols by ultrahigh‐performance liquid chromatography/tandem mass spectrometry 下载免费PDF全文