In-vitro metabolic profiling study of potential topoisomerase inhibitors ‘pyrazolines’ in RLMs by mass spectrometry

Kadi, Adnan A.; Yin, Wencui; Rahman, A. F. M. Motiur

doi:10.1016/j.jchromb.2019.03.026

Cited by 6 publications

(5 citation statements)

References 20 publications

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“…In this regard, high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometry (MS) predominates over all other analytical tools used for screening and characterizing metabolites. MS detectors including ion trap and triple quadrupole (QqQ) have been widely used for the detection and characterization of metabolites that were generated either in vitro or in vivo due to their high selectivity and sensitivity [34][35][36][37].…”

Section: Introductionmentioning

confidence: 99%

Simvastatin: In Vitro Metabolic Profiling of a Potent Competitive HMG-CoA Reductase Inhibitor

et al. 2022

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Simvastatin (SV) is a semisynthetic derivative of lovastatin (LV), which is biosynthetically produced from the fungus Aspergillus terreus and has a high log p value (log p = 4.39)and thus high hepatic extraction and high efficacy in controlling cholesterol synthesis. The current study was undertaken to investigate the metabolic profile of SV using various mass spectrometry (MS) platforms. Metabolic profiling was studied in in vitro models, rat liver microsomes (RLMs), and isolated perfused rat liver hepatocytes (RLHs) using both ion trap and triple quadruple LC–MS/MS systems. A total of 29 metabolites were identified. Among them, three types of SV-related phase-I metabolites, namely exomethylene simvastatin acid (exomethylene SVA), monohydroxy SVA, and dihydrodiol SVA, were identified as new in RLMs. No phase-II metabolites were identified while incubating with RLHs.

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Section: Introductionmentioning

confidence: 99%

Simvastatin: In Vitro Metabolic Profiling of a Potent Competitive HMG-CoA Reductase Inhibitor

et al. 2022

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“…[5] Presently, a large number of synthetic heterocycles are reported as the potential drug molecules with potent bioactivities. [6] Most of the marketed drugs are found to contain at least one heterocyclic moiety in their structural framework. The presence of such heterocyclic nucleus seems to be responsible to enhance their ability for the salt formation and solubility properties that help to enable them for their easy bioavailability.…”

Section: Introductionmentioning

confidence: 99%

“…Heterocyclic compounds have been used for the treatment of several infectious diseases owing to their inherent toxicity toward various pathogens . Presently, a large number of synthetic heterocycles are reported as the potential drug molecules with potent bioactivities . Most of the marketed drugs are found to contain at least one heterocyclic moiety in their structural framework.…”

Section: Introductionmentioning

confidence: 99%

Synthetic and antimicrobial studies of N‐substituted‐pyrazoline‐based new bisheterocycles

Nisa

Yusuf

2020

Journal of Heterocyclic Chem

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In the present study, the four series of N‐acetyl/N‐carbothioamide/N‐carboxamide/N‐phenyl‐based new bispyrazolines have been synthesized. These symmetrical bisheterocyclic products were prepared efficiently from the ring‐closure reactions of new bischalcones 2a‐d with appropriate cyclizing agents (hydrazine hydrate, thiosemicarbazide, semicarbazide, and phenyl hydrazine) under the alkaline ethanolic conditions. The compounds 2a‐d were obtained by treating hydroxyl‐substituted chalcone 1 with various dihalogenated reagents (α,α′‐dibromo‐o/m/p‐xylene and 4,4′‐bischloromethyl‐diphenyl) in anhydrous K2CO3/dry acetone/Bu4N+I− medium. The structures of all the newly synthesized products have been authenticated with the help of their IR, 1H‐NMR, 13C‐NMR, and ESI‐MS spectral data and their purity was corroborated with the help of elemental analysis and thin‐layer chromatography results. The in vitro antimicrobial screening of the newly synthesized intermediates and final bisheterocycles has also been performed by using the serial tube dilution technique against the selected number of microorganisms. The final bisheterocycles revealed better antibacterial and antifungal potencies as compared to their corresponding bischalcones. Among the symmetrical bisheterocyclic products, N‐acetyl and N‐carbothioamide‐substituted bispyrazolines were found to exhibit potential antimicrobial properties than the other products.

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“…The proteoform in each immunoreactive positive spot was subjected to in-gel digestion with trypsin, and identification with MS [17,18]. MS is a key technique to identify organic molecules and analyze the extreme structure of certain substances [19]. Especially, top-down MS can quickly and extremely accurately determine the molecular weight of biomacromolecules, which enables proteomics research from protein general identification to advanced structural studies and protein-protein interaction studies.…”

Section: Introductionmentioning

confidence: 99%

Prolactin Proteoform Pattern Changed in Human Pituitary Adenoma Relative to Control Pituitary Tissues

Zhan¹,

Qian²

2020

Proteoforms - Concept and Applications in Medical Sciences

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PRL gene-encoded prolactin is synthesized in the ribosome in the pituitary and then secretes into blood circulation to reach its target organ and exerts its biological roles, for example, involving in production, growth, development, immunoregulation, and metabolism. Multiple post-translational modifications and other unknown factors might be involved in this process to cause different prolactin proteoforms with differential isoelectric point (pI) and relative mass (M r). Pituitary adenomas are the common disease occurring in pituitary organ to affect the endocrine system. Two-dimensional gel electrophoresis (2DGE) was used to separate prolactin proteoforms according to their pI and M r , followed by identification with Western blot and mass spectrometry (MS) analyses. Six prolactin proteoforms were identified in control pituitary tissues, and this prolactin proteoform pattern was significantly changed in different hormone subtypes of nonfunctional pituitary adenomas (NF − , LH + , FSH + , and LH + / FSH +) and prolactinomas (PRL +). Further, bioinformatics analysis revealed that different prolactin proteoforms might bind to different short-or long-PRL receptor-mediated signaling pathways. These findings clearly demonstrated that prolactin proteoform pattern existed in human pituitary and changed in different subtypes of pituitary adenomas. It is the scientific data to in-depth study prolactin functions, and to discover the prolactin proteoform biomarkers for PRL-related adenomas.

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In-vitro metabolic profiling study of potential topoisomerase inhibitors ‘pyrazolines’ in RLMs by mass spectrometry

Cited by 6 publications

References 20 publications

Simvastatin: In Vitro Metabolic Profiling of a Potent Competitive HMG-CoA Reductase Inhibitor

Simvastatin: In Vitro Metabolic Profiling of a Potent Competitive HMG-CoA Reductase Inhibitor

Synthetic and antimicrobial studies of N‐substituted‐pyrazoline‐based new bisheterocycles

Prolactin Proteoform Pattern Changed in Human Pituitary Adenoma Relative to Control Pituitary Tissues

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