Novel Antiproliferative Biphenyl Nicotinamide: NMR Metabolomic Study of its Effect on the MCF-7 Cell in Comparison with Cisplatin and Vinblastine
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Title: | Novel Antiproliferative Biphenyl Nicotinamide: NMR Metabolomic Study of its Effect on the MCF-7 Cell in Comparison with Cisplatin and Vinblastine |
Author: | Coco, Laura del Majellaro, María Boccarelli, Angelina Cellamare, Saverio Altomare, Cosimo Damiano Fanizzi, Francesco Paolo |
Affiliation: | Universidade de Santiago de Compostela. Centro de Investigación en Química Biolóxica e Materiais Moleculares Universidade de Santiago de Compostela. Departamento de Química Orgánica |
Subject: | Biaryl nicotinamide | Breast cancer | Antiproliferative activity | Metabolomics | NMR spectroscopy | MVA | |
Date of Issue: | 2020 |
Publisher: | MDPI |
Citation: | Del Coco, L.; Majellaro, M.; Boccarelli, A.; Cellamare, S.; Altomare, C.D.; Fanizzi, F.P. Novel Antiproliferative Biphenyl Nicotinamide: NMR Metabolomic Study of its Effect on the MCF-7 Cell in Comparison with Cisplatin and Vinblastine. Molecules 2020, 25, 3502 |
Abstract: | A 1H-NMR-based metabolomic study was performed on MCF-7 cell lines treated with a novel nicotinamide derivative (DT-8) in comparison with two drugs characterized by a well-established mechanism of action, namely the DNA-metalating drug cisplatin (cis-diamminedichloridoplatinum(II), CDDP) and the antimitotic drug vinblastine (vinblastine, VIN). The effects of the three compounds, each one at the concentration corresponding to the IC50 value, were investigated, with respect to the controls (K), by the 1H-NMR of cells lysates and multivariate analysis (MVA) of the spectroscopic data. Relevant differences were found in the metabolic profiles of the different treatments with respect to the controls. A large overlap of the metabolic profiles in DT-8 vs. K and VIN vs. K suggests a similar biological response and mechanism of action, significantly diverse with respect to CDDP. On the other hand, DT8 seems to act by disorganizing the mitotic spindle and ultimately blocking the cell division, through a mechanism implying methionine depletion and/or S-adenosylmethionine (SAM) limitation |
Publisher version: | https://doi.org/10.3390/molecules25153502 |
URI: | http://hdl.handle.net/10347/23528 |
DOI: | 10.3390/molecules25153502 |
E-ISSN: | 1420-3049 |
Rights: | © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/) Atribución 4.0 Internacional |
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Except where otherwise noted, this item's license is described as © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)