Probing the Mechanism of Action of Potential Anticancer Agents at a Molecular Level Using Electrospray Ionisation Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

2009 ◽  
Vol 15 (5) ◽  
pp. 661-672 ◽  
Author(s):  
Lutz F. Tietze ◽  
Birgit Krewer ◽  
Holm Frauendorf
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Anticancer Agents ◽  
Mode Of Action ◽  
Molecular Level ◽  
High Resolution Mass Spectrometry ◽  
New Drugs ◽  
Duplex Dna ◽  
High Resolution Mass ◽  
Resolution Mass

Treating cancer without harming healthy tissue is an important goal in modern medicine. Our research group has developed a series of novel, relatively non-toxic glycosidic prodrugs that are activated to give the corresponding highly cytotoxic drugs selectively in the tumour tissue. Our first investigations have shown a high duplex DNA alkylation efficiency of the drugs, whereas the prodrugs showed almost no tendency for alkylation of duplex DNA. Herein we report on novel investigations of the mode of action of the anti-cancer drugs on a molecular level. Using high-resolution mass spectrometry, we determined the reactivity of these drugs as well as of other drugs of similar structure against different nucleophiles such as RNA and the tripeptide glutathione. In addition, the new drugs were also tested for their interaction with duplex DNA. All compounds show a high reactivity against duplex DNA, whereas the alkylation efficiency regarding RNA and glutathione is only poor. Furthermore, the alkylation of duplex DNA correlates qualitatively but not quantitatively with the cytotoxicity of the drugs. Consequently, other factors besides the alkylation efficiency such as the stability of the drugs seem to influence their biological activity. Altogether the results show that high-resolution mass spectrometry constitutes a powerful method for studying the mode of action of drugs on a molecular level.

Molecular-level heavy petroleum hydrotreating modeling and comparison with high-resolution mass spectrometry

Fuel ◽  
2021 ◽  
Vol 297 ◽  
pp. 120792
Author(s):  
Dong Guan ◽  
Zhengyu Chen ◽  
Xiu Chen ◽  
Ying Zhang ◽  
Qiuyan Qi ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Molecular Level ◽  
High Resolution Mass Spectrometry ◽  
Heavy Petroleum ◽  
High Resolution Mass ◽  
Resolution Mass

Molecular-Level Characterization of Refinery Streams by High-Resolution Mass Spectrometry

2015 ◽  
Vol 29 (5) ◽  
pp. 2940-2950 ◽  
Author(s):  
Vatsala Sugumaran ◽  
Hillol Biswas ◽  
Anil Yadav ◽  
Jayaraj Christopher ◽  
Vivekanand Kagdiyal ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Molecular Level ◽  
High Resolution Mass Spectrometry ◽  
High Resolution Mass ◽  
Resolution Mass

Chemical fractionation of a terrestrial humic acid upon sorption on alumina by high resolution mass spectrometry

RSC Advances ◽  
2015 ◽  
Vol 5 (89) ◽  
pp. 73058-73067 ◽  
Author(s):  
Catherine Galindo ◽  
Mirella Del Nero
Keyword(s):  
Mass Spectrometry ◽  
Humic Acid ◽  
High Resolution ◽  
Molecular Level ◽  
High Resolution Mass Spectrometry ◽  
Chemical Fractionation ◽  
High Resolution Mass ◽  
Resolution Mass

Using mass spectrometry provided molecular-level insights into the chemical fractionation, and identity of adsorbed compounds, for a terrestrial humic acid rich in condensed aromatics, in alumina-solution systems.

Exploring the Active Compounds of Traditional Mongolian Medicine Agsirga in Intervention of Novel Coronavirus (2019-nCoV) Based on HPLC-Q-Exactive-MS/MS and Molecular Docking Method

2020 ◽  
Author(s):  
Jie Cheng ◽  
Yuchen Tang ◽  
Baoquan Bao ◽  
Ping Zhang
Keyword(s):  
Mass Spectrometry ◽  
Molecular Docking ◽  
High Resolution ◽  
Mass Spectra ◽  
High Resolution Mass Spectrometry ◽  
Structural Formula ◽  
Active Compounds ◽  
High Resolution Mass ◽  
Q Exactive ◽  
Resolution Mass

<p><a></a><a></a><a></a><a><b>Objective</b></a>: To screen all compounds of Agsirga based on the HPLC-Q-Exactive high-resolution mass spectrometry and find potential inhibitors that can respond to 2019-nCoV from active compounds of Agsirga by molecular docking technology.</p> <p><b>Methods</b>: HPLC-Q-Exactive high-resolution mass spectrometry was adopted to identify the complex components of Mongolian medicine Agsirga, and separated by the high-resolution mass spectrometry Q-Exactive detector. Then the Orbitrap detector was used in tandem high-resolution mass spectrometry, and the related molecular and structural formula were found by using the chemsipider database and related literature, combined with precise molecular formulas (errors ≤ 5 × 10<sup>−6</sup>) , retention time, primary mass spectra, and secondary mass spectra information, The fragmentation regularities of mass spectra of these compounds were deduced. Taking ACE2 as the receptor and deduced compounds as the ligand, all of them were pretreated by discover studio, autodock and Chem3D. The molecular docking between the active ingredients and the target protein was studied by using AutoDock molecular docking software. The interaction between ligand and receptor is applied to provide a choice for screening anti-2019-nCoV drugs.</p> <p><b>Result</b>: Based on the fragmentation patterns of the reference compounds and consulting literature, a total of 96 major alkaloids and stilbenes were screened and identified in Agsirga by the HPLC-Q-Exactive-MS/MS method. Combining with molecular docking, a conclusion was got that there are potential active substances in Mongolian medicine Agsirga which can block the binding of ACE2 and 2019-nCoV at the molecular level.</p>

Determination of quaternary ammonium compounds in food products by the method of ultra-performance liquid chromatography/high resolution mass-spectrometry

2020 ◽  
Vol 86 (8) ◽  
pp. 23-31
Author(s):  
V. G. Amelin ◽  
D. S. Bolshakov
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Quaternary Ammonium ◽  
High Resolution Mass Spectrometry ◽  
Food Products ◽  
Quaternary Ammonium Compounds ◽  
High Resolution Mass ◽  
Ammonium Compounds ◽  
Resolution Mass

The goal of the study is developing a methodology for determination of the residual amounts of quaternary ammonium compounds (QAC) in food products by UHPLC/high-resolution mass spectrometry after water-acetonitrile extraction of the determined components from the analyzed samples. The identification and determination of QAC was carried out on an «UltiMate 3000» ultra-high-performance liquid chromatograph (Thermo Scientific, USA) equipped with a «maXis 4G» high-resolution quadrupole-time-of-flight mass spectrometric detector and an ion spray «ionBooster» source (Bruker Daltonics, Germany). Samples of milk, cheese (upper cortical layer), dumplings, pork, chicken skin and ground beef were used as working samples. Optimal conditions are specified for chromatographic separation of the mixture of five QAC, two of them being a mixture of homologues with a linear structure (including isomeric forms). The identification of QAC is carried out by the retention time, exact mass of the ions, and coincidence of the mSigma isotopic distribution. The limits for QAC detection are 0.1 – 0.5 ng/ml, the determination limits are 1 ng/ml for aqueous standard solutions. The determinable content of QAC in food products ranges within 1 – 100 ng/g. The results of analysis revealed the residual amount of QAC present in all samples, which confirms data of numerous sources of information about active use of QAC-based disinfectants in the meat and dairy industry. The correctness of the obtained results is verified by introduction of the additives in food products at a level of 10 ng/g for each QAC. The relative standard deviation of the analysis results does not exceed 0.18. The duration of the analysis is 30 – 40 min.

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