Applications of Nuclear Magnetic Resonance and Mass Spectrometry to Anticancer Drug Discovery

Powers, Robert; Siegel, Marshall M.

doi:10.1016/b978-012088561-9/50006-5

Cited by 8 publications

(3 citation statements)

References 329 publications

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“…Currently, the widely applied metabonomics research methods include Nuclear Magnetic Resonance (NMR), GC-TOF/MS, and UPLCQ-TOF/MS ( 14 , 15 ). In comparison, nuclear magnetic resonance (NMR) technology is widely used for its advantages of non-destructive, absolute quantitative, and outstanding repeatability ( 16 ).…”

Section: Discussionmentioning

confidence: 99%

Impacts of Colored Light-Emitting Diode Illumination on the Reproductive Performance and Bioactive Constituents and the Molecular Mechanism of Hypothalamus Gland in Zi-geese

et al. 2022

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Goose is a seasonal breeding animal. Its reproduction is regulated by hypothalamus-pituitary-gonad axis and also affected by environmental factors such as light and location. Zi-goose is characterized with long egg-laying period and high egg-laying potential and belongs to the long-day type of seasonal breeding. In this study, the regulation mechanism of different lighting on reproductive performance of Zi-goose by using metabonomics analysis technology. In addition, 1,481 differential metabolites were screened out totally. 583 differential metabolites were identification in hypothalamus of Zi-goose. 196 differential metabolites were identification in pituitary of Zi-goose. 692 differential metabolites were identification in ovary of Zi-goose. Under red light condition for 12 h, expression of 433 differential metabolites were down-regulated and expression of 150 differential metabolites were up regulated in hypothalamus of Zi-goose, expression of 125 differential metabolites were down-regulated and expression of 71 differential metabolites were up-regulated in pituitary of Zi-goose, expression of 355 differential metabolites were down-regulated and expression of 337 differential metabolites were up-regulated in ovary of Zi-goose. 33 differential metabolites were closely associated with 1,264 transcripts and 400 homologous genes of related enzymes in hypothalamus of Zi-goose. 15 differential metabolites were closely associated with 163 transcripts and 47 homologous genes of related enzymes in pituitary of Zi-goose. 55 differential metabolites were closely associated with 1,255 transcripts and 360 homologous genes of related enzymes in ovary of Zi-goose. It was confirmed that four metabolic pathways were closely related to light regulation of reproductive performance of Zi-goose, namely GnRH signaling pathway, prolactin signaling pathway, thyroid hormone synthesis and ovarian steroidogenesis. Typical differential metabolites of arachidonic acid, glucose-6-phosphate, progesterone, glutathione, oxidized glutathione, testosterone, deoxyepiandrosterone and their related protein genes would play an important role in light regulation of reproductive performance of Zi-goose.

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Section: Discussionmentioning

confidence: 99%

Impacts of Colored Light-Emitting Diode Illumination on the Reproductive Performance and Bioactive Constituents and the Molecular Mechanism of Hypothalamus Gland in Zi-geese

et al. 2022

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“…При конструировании химиотерапевтических препаратов испытывались вещества с разной структурой, которые могли воздействовать на ДНК по различным механизмам. Выделяют три основных вида взаимодействия противораковых агентов с ДНК: модификация азотистых оснований ДНК посредством химических реакций, невалентные взаимодействия путем встраивания (интеркаляции) плоских частей молекул препаратов между парами оснований и/или укладки молекул в бороздки двойной спирали ДНК [26]. В рамках междисциплинарных комплексных исследований, проводившихся во всем мире, необходимо было получить прямые доказательства ковалентных или невалентных взаимодействий препаратов с молекулой ДНК, и биофизики ФТИНТ приняли активное участие в решении этой задачи.…”

Section: взаимодействие алкилирующих противоопухолевых препаратов сunclassified

Biophysical investigations of molecular mechanisms of chemotherapeutic agents action. 1. Chemotherapeutic and antiviral agents (Review)

2019

Biophysical Bulletin

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Background: Determination of molecular mechanisms of action of drugs forms a scientific basis for the directed search of efficient medications. Assumed pathways of interactions of chemotherapeutic drugs which affect infectious agents and malignant neoplasm with their potential molecular targets require direct evidences at the molecular level. Such evidences can be obtained by means of molecular biophysics which possesses an arsenal of new powerful physical techniques for studying the intermolecular interactions of biomolecules and pharmaceutical agents. Objectives: The aim of this review is the generalization of the results of long standing investigations on the molecular mechanisms of action of chemotherapeutic agents performed in the biophysical departments of B. Verkin Institute for Low Temperature Physics and Engineering (ILTPE) of the NAS of Ukraine. The first part of the review is devoted to anticancer and antiviral agents targeted presumably at nucleic acids. Materials and methods: Mass spectrometric studies of molecules of thermally unstable drugs and their complexes with biomolecules have been advanced significantly due to the development of soft ionization/desorption techniques; the researchers of ILTPE have made noticeable contribution to this field. The methods of molecular spectroscopy and computer modeling by means of quantum chemistry were applied in the combined investigations. Results: The objects of study were the systems composed of chemotherapeutic drugs – thiophosphamide, phenazine derivatives and phenazine-modified antigene/antisense oligonucleotides, quaternary compounds, tilorone – and their molecular targets – DNA, oligo- and polynucleotides and nucleic acids components. The mechanisms of action of these drugs established at the model molecular level consisted in the specific and nonspecific noncovalent or covalent interactions of the drugs’ molecules with nucleic acids and their components and in the formation of stable drug-target complexes. Conclusions: The experience of investigations conducted during several decades at the ILTPE has demonstrated the efficiency of the application of the methods and approaches of molecular biophysics to establishing of molecular mechanisms of drugs action. The basic results obtained are of practical importance for the further development of new efficient pharmaceuticals.

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“…Mass spectrometry has been widely used for the quantification and identification of pharmaceuticals 13,14 . Using collision‐induced dissociation tandem mass spectrometry (CID‐MS/MS), the fragmentation pattern of structurally related compounds can be established 15,16 .…”

Section: Introductionmentioning

confidence: 99%

Establishment of the tandem mass spectrometric fingerprints of taxane‐based anticancer compounds

Khajavinia

Haddadi

El‐Aneed

2021

Rapid Comm Mass Spectrometry

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Rationale Compounds in the taxane drug family are among the most successful and effective chemotherapeutic agents used in the treatment of solid tumors, such as breast, ovarian, and prostate cancers. The tandem mass spectrometric (MS/MS) fragmentation behavior of these compounds is described in detail, and a generalized MS/MS fingerprint is established for the first time. Methods Five compounds, namely paclitaxel, docetaxel, cabazitaxel, cephalomannine, and baccatin III, were evaluated. A hybrid quadrupole orthogonal time‐of‐flight (Q‐TOF) mass spectrometer was used to obtain accurate mass measurements, whereas MS/MS and second‐generation MS/MS (MS3) analyses were performed using a triple quadrupole‐linear ion trap mass spectrometer. Both instruments were equipped with an electrospray ionization source operated in the positive ion mode. Results All taxanes showed an abundant singly charged [M + H]+ species in the single‐stage analysis with mass accuracies less than 3 ppm. The evaluated compounds exhibited common fragmentation behavior in their MS/MS analysis, which allowed for the production of a universal fragmentation pattern. MS3 experiments confirmed the genesis of the various product ions proposed in the fragmentation pathway. In addition, diagnostic product ions were originated from a cleavage in the ester bond between the core diterpene ring structure and the side chain. Conclusions Varying functional groups present in these compounds resulted in unique product ions that are specific to each structure. The established MS/MS fingerprints will be used in the near future for identification and for the development of multiple reaction monitoring liquid chromatography–MS/MS quantification methods.

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Applications of Nuclear Magnetic Resonance and Mass Spectrometry to Anticancer Drug Discovery

Cited by 8 publications

References 329 publications

Impacts of Colored Light-Emitting Diode Illumination on the Reproductive Performance and Bioactive Constituents and the Molecular Mechanism of Hypothalamus Gland in Zi-geese

Impacts of Colored Light-Emitting Diode Illumination on the Reproductive Performance and Bioactive Constituents and the Molecular Mechanism of Hypothalamus Gland in Zi-geese

Biophysical investigations of molecular mechanisms of chemotherapeutic agents action. 1. Chemotherapeutic and antiviral agents (Review)

Establishment of the tandem mass spectrometric fingerprints of taxane‐based anticancer compounds

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