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Theoretical Investigations and Density Functional Theory Based Quantitative Structure–Activity Relationships Model for Novel Cytotoxic Platinum(IV) Complexes
[Image: see text] Octahedral platinum(IV) complexes are promising candidates in the fight against cancer. In order to rationalize the further development of this class of compounds, detailed studies on their mechanisms of action, toxicity, and resistance must be provided and structure–activity relat...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2012
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557934/ https://www.ncbi.nlm.nih.gov/pubmed/23214999 http://dx.doi.org/10.1021/jm3016427 |
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author | Varbanov, Hristo P. Jakupec, Michael A. Roller, Alexander Jensen, Frank Galanski, Markus Keppler, Bernhard K. |
author_facet | Varbanov, Hristo P. Jakupec, Michael A. Roller, Alexander Jensen, Frank Galanski, Markus Keppler, Bernhard K. |
author_sort | Varbanov, Hristo P. |
collection | PubMed |
description | [Image: see text] Octahedral platinum(IV) complexes are promising candidates in the fight against cancer. In order to rationalize the further development of this class of compounds, detailed studies on their mechanisms of action, toxicity, and resistance must be provided and structure–activity relationships must be drawn. Herein, we report on theoretical and QSAR investigations of a series of 53 novel bis-, tris-, and tetrakis(carboxylato)platinum(IV) complexes, synthesized and tested for cytotoxicity in our laboratories. The hybrid DFT functional wb97x was used for optimization of the structure geometry and calculation of the descriptors. Reliable and robust QSAR models with good explanatory and predictive properties were obtained for both the cisplatin sensitive cell line CH1 and the intrinsically cisplatin resistant cell line SW480, with a set of four descriptors. |
format | Online Article Text |
id | pubmed-3557934 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-35579342013-01-31 Theoretical Investigations and Density Functional Theory Based Quantitative Structure–Activity Relationships Model for Novel Cytotoxic Platinum(IV) Complexes Varbanov, Hristo P. Jakupec, Michael A. Roller, Alexander Jensen, Frank Galanski, Markus Keppler, Bernhard K. J Med Chem [Image: see text] Octahedral platinum(IV) complexes are promising candidates in the fight against cancer. In order to rationalize the further development of this class of compounds, detailed studies on their mechanisms of action, toxicity, and resistance must be provided and structure–activity relationships must be drawn. Herein, we report on theoretical and QSAR investigations of a series of 53 novel bis-, tris-, and tetrakis(carboxylato)platinum(IV) complexes, synthesized and tested for cytotoxicity in our laboratories. The hybrid DFT functional wb97x was used for optimization of the structure geometry and calculation of the descriptors. Reliable and robust QSAR models with good explanatory and predictive properties were obtained for both the cisplatin sensitive cell line CH1 and the intrinsically cisplatin resistant cell line SW480, with a set of four descriptors. American Chemical Society 2012-12-10 2013-01-10 /pmc/articles/PMC3557934/ /pubmed/23214999 http://dx.doi.org/10.1021/jm3016427 Text en Copyright © 2012 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) |
spellingShingle | Varbanov, Hristo P. Jakupec, Michael A. Roller, Alexander Jensen, Frank Galanski, Markus Keppler, Bernhard K. Theoretical Investigations and Density Functional Theory Based Quantitative Structure–Activity Relationships Model for Novel Cytotoxic Platinum(IV) Complexes |
title | Theoretical Investigations
and Density Functional Theory Based Quantitative Structure–Activity
Relationships Model for Novel Cytotoxic Platinum(IV) Complexes |
title_full | Theoretical Investigations
and Density Functional Theory Based Quantitative Structure–Activity
Relationships Model for Novel Cytotoxic Platinum(IV) Complexes |
title_fullStr | Theoretical Investigations
and Density Functional Theory Based Quantitative Structure–Activity
Relationships Model for Novel Cytotoxic Platinum(IV) Complexes |
title_full_unstemmed | Theoretical Investigations
and Density Functional Theory Based Quantitative Structure–Activity
Relationships Model for Novel Cytotoxic Platinum(IV) Complexes |
title_short | Theoretical Investigations
and Density Functional Theory Based Quantitative Structure–Activity
Relationships Model for Novel Cytotoxic Platinum(IV) Complexes |
title_sort | theoretical investigations
and density functional theory based quantitative structure–activity
relationships model for novel cytotoxic platinum(iv) complexes |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557934/ https://www.ncbi.nlm.nih.gov/pubmed/23214999 http://dx.doi.org/10.1021/jm3016427 |
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