1.
Braga, Scheila Furtado; Galvao, Douglas Soares
A structure-activity study of taxol, taxotere, and derivatives using the electronic indices methodology (EIM) Journal Article
In: Journal of chemical information and computer sciences, vol. 43, no. 2, pp. 699–706, 2003.
@article{braga2003structure,
title = {A structure-activity study of taxol, taxotere, and derivatives using the electronic indices methodology (EIM)},
author = {Braga, Scheila Furtado and Galvao, Douglas Soares},
url = {http://pubs.acs.org/doi/abs/10.1021/ci025640v},
year = {2003},
date = {2003-01-01},
journal = {Journal of chemical information and computer sciences},
volume = {43},
number = {2},
pages = {699--706},
publisher = {American Chemical Society},
abstract = {Among the new families of effective anticancer drugs, the natural product paclitaxel (Taxol/Bristol-MyersSquibb)
and its semisynthetic derivative docetaxel (Taxotere/Rhone-Poulenc Rorer) are probably the most
promising agents under investigation. Surprisingly considering their importance no detailed quantum
mechanical studies have been carried out for these drugs. In this work we report the first structure-activity
relationship (SAR) studies for 20 taxoid structures using molecular descriptors from all-electron quantum
methods. The used methods were the pattern-recognition Principal Component Analysis (PCA), Hierarchical
Clustering Analysis (HCA), and the recently developed Electronic Indices Methodology (EIM). The combined
use of EIM with PCA/HCA methodologies was able to correctly classify active and inactive taxoids with
100% of accuracy using only a few “universal” quantum molecular descriptors. It was possible to identify
the electronic features defining active molecules. This information can be used to select and design new
active compounds. The combined use of EIM with PCA/HCA can be a new and very efficient tool in the
field of computer assisted drug design.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Among the new families of effective anticancer drugs, the natural product paclitaxel (Taxol/Bristol-MyersSquibb)
and its semisynthetic derivative docetaxel (Taxotere/Rhone-Poulenc Rorer) are probably the most
promising agents under investigation. Surprisingly considering their importance no detailed quantum
mechanical studies have been carried out for these drugs. In this work we report the first structure-activity
relationship (SAR) studies for 20 taxoid structures using molecular descriptors from all-electron quantum
methods. The used methods were the pattern-recognition Principal Component Analysis (PCA), Hierarchical
Clustering Analysis (HCA), and the recently developed Electronic Indices Methodology (EIM). The combined
use of EIM with PCA/HCA methodologies was able to correctly classify active and inactive taxoids with
100% of accuracy using only a few “universal” quantum molecular descriptors. It was possible to identify
the electronic features defining active molecules. This information can be used to select and design new
active compounds. The combined use of EIM with PCA/HCA can be a new and very efficient tool in the
field of computer assisted drug design.
and its semisynthetic derivative docetaxel (Taxotere/Rhone-Poulenc Rorer) are probably the most
promising agents under investigation. Surprisingly considering their importance no detailed quantum
mechanical studies have been carried out for these drugs. In this work we report the first structure-activity
relationship (SAR) studies for 20 taxoid structures using molecular descriptors from all-electron quantum
methods. The used methods were the pattern-recognition Principal Component Analysis (PCA), Hierarchical
Clustering Analysis (HCA), and the recently developed Electronic Indices Methodology (EIM). The combined
use of EIM with PCA/HCA methodologies was able to correctly classify active and inactive taxoids with
100% of accuracy using only a few “universal” quantum molecular descriptors. It was possible to identify
the electronic features defining active molecules. This information can be used to select and design new
active compounds. The combined use of EIM with PCA/HCA can be a new and very efficient tool in the
field of computer assisted drug design.
2.
Braga, SF; Galvao, DS
A semiempirical study on the electronic structure of 10-deacetylbaccatin-III Journal Article
In: Journal of Molecular Graphics and Modelling, vol. 21, no. 1, pp. 57–70, 2002.
@article{braga2002semiempirical,
title = {A semiempirical study on the electronic structure of 10-deacetylbaccatin-III},
author = {Braga, SF and Galvao, DS},
url = {http://www.sciencedirect.com/science/article/pii/S1093326302001213},
year = {2002},
date = {2002-01-01},
journal = {Journal of Molecular Graphics and Modelling},
volume = {21},
number = {1},
pages = {57--70},
publisher = {Elsevier},
abstract = {We performed a conformational and electronic analysis for 10-deacetylbaccatin-III (DBAC) using well-known semiempirical methods (parametric method 3 (PM3) and Zerner’s intermediate neglect of differential overlap (ZINDO)) coupled to the concepts of total and local density of states (LDOS). Our results indicate that regions presented by paclitaxel (Taxol®) as important for the biological activity can be traced out by the electronic features present in DBAC. These molecules differ only by a phenylisoserine side chain. Compared to paclitaxel, DBAC has a simpler structure in terms of molecular size and number of degrees of freedom (d.f.). This makes DBAC a good candidate for a preliminary investigation of the taxoid family. Our results question the importance of the oxetane group, which seems to be consistent with recent experimental data.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We performed a conformational and electronic analysis for 10-deacetylbaccatin-III (DBAC) using well-known semiempirical methods (parametric method 3 (PM3) and Zerner’s intermediate neglect of differential overlap (ZINDO)) coupled to the concepts of total and local density of states (LDOS). Our results indicate that regions presented by paclitaxel (Taxol®) as important for the biological activity can be traced out by the electronic features present in DBAC. These molecules differ only by a phenylisoserine side chain. Compared to paclitaxel, DBAC has a simpler structure in terms of molecular size and number of degrees of freedom (d.f.). This makes DBAC a good candidate for a preliminary investigation of the taxoid family. Our results question the importance of the oxetane group, which seems to be consistent with recent experimental data.
2003
2.
Braga, Scheila Furtado; Galvao, Douglas Soares
A structure-activity study of taxol, taxotere, and derivatives using the electronic indices methodology (EIM) Journal Article
In: Journal of chemical information and computer sciences, vol. 43, no. 2, pp. 699–706, 2003.
Abstract | Links | BibTeX | Tags: Drug Design, Electronic Structure, Taxol, Taxotere, Theory of Electronic Indices
@article{braga2003structure,
title = {A structure-activity study of taxol, taxotere, and derivatives using the electronic indices methodology (EIM)},
author = {Braga, Scheila Furtado and Galvao, Douglas Soares},
url = {http://pubs.acs.org/doi/abs/10.1021/ci025640v},
year = {2003},
date = {2003-01-01},
journal = {Journal of chemical information and computer sciences},
volume = {43},
number = {2},
pages = {699--706},
publisher = {American Chemical Society},
abstract = {Among the new families of effective anticancer drugs, the natural product paclitaxel (Taxol/Bristol-MyersSquibb)
and its semisynthetic derivative docetaxel (Taxotere/Rhone-Poulenc Rorer) are probably the most
promising agents under investigation. Surprisingly considering their importance no detailed quantum
mechanical studies have been carried out for these drugs. In this work we report the first structure-activity
relationship (SAR) studies for 20 taxoid structures using molecular descriptors from all-electron quantum
methods. The used methods were the pattern-recognition Principal Component Analysis (PCA), Hierarchical
Clustering Analysis (HCA), and the recently developed Electronic Indices Methodology (EIM). The combined
use of EIM with PCA/HCA methodologies was able to correctly classify active and inactive taxoids with
100% of accuracy using only a few “universal” quantum molecular descriptors. It was possible to identify
the electronic features defining active molecules. This information can be used to select and design new
active compounds. The combined use of EIM with PCA/HCA can be a new and very efficient tool in the
field of computer assisted drug design.},
keywords = {Drug Design, Electronic Structure, Taxol, Taxotere, Theory of Electronic Indices},
pubstate = {published},
tppubtype = {article}
}
Among the new families of effective anticancer drugs, the natural product paclitaxel (Taxol/Bristol-MyersSquibb)
and its semisynthetic derivative docetaxel (Taxotere/Rhone-Poulenc Rorer) are probably the most
promising agents under investigation. Surprisingly considering their importance no detailed quantum
mechanical studies have been carried out for these drugs. In this work we report the first structure-activity
relationship (SAR) studies for 20 taxoid structures using molecular descriptors from all-electron quantum
methods. The used methods were the pattern-recognition Principal Component Analysis (PCA), Hierarchical
Clustering Analysis (HCA), and the recently developed Electronic Indices Methodology (EIM). The combined
use of EIM with PCA/HCA methodologies was able to correctly classify active and inactive taxoids with
100% of accuracy using only a few “universal” quantum molecular descriptors. It was possible to identify
the electronic features defining active molecules. This information can be used to select and design new
active compounds. The combined use of EIM with PCA/HCA can be a new and very efficient tool in the
field of computer assisted drug design.
and its semisynthetic derivative docetaxel (Taxotere/Rhone-Poulenc Rorer) are probably the most
promising agents under investigation. Surprisingly considering their importance no detailed quantum
mechanical studies have been carried out for these drugs. In this work we report the first structure-activity
relationship (SAR) studies for 20 taxoid structures using molecular descriptors from all-electron quantum
methods. The used methods were the pattern-recognition Principal Component Analysis (PCA), Hierarchical
Clustering Analysis (HCA), and the recently developed Electronic Indices Methodology (EIM). The combined
use of EIM with PCA/HCA methodologies was able to correctly classify active and inactive taxoids with
100% of accuracy using only a few “universal” quantum molecular descriptors. It was possible to identify
the electronic features defining active molecules. This information can be used to select and design new
active compounds. The combined use of EIM with PCA/HCA can be a new and very efficient tool in the
field of computer assisted drug design.
2002
1.
Braga, SF; Galvao, DS
A semiempirical study on the electronic structure of 10-deacetylbaccatin-III Journal Article
In: Journal of Molecular Graphics and Modelling, vol. 21, no. 1, pp. 57–70, 2002.
Abstract | Links | BibTeX | Tags: Baccatin, Drug Design, Electronic Structure, Taxol, Taxotere, Theory of Electronic Indices
@article{braga2002semiempirical,
title = {A semiempirical study on the electronic structure of 10-deacetylbaccatin-III},
author = {Braga, SF and Galvao, DS},
url = {http://www.sciencedirect.com/science/article/pii/S1093326302001213},
year = {2002},
date = {2002-01-01},
journal = {Journal of Molecular Graphics and Modelling},
volume = {21},
number = {1},
pages = {57--70},
publisher = {Elsevier},
abstract = {We performed a conformational and electronic analysis for 10-deacetylbaccatin-III (DBAC) using well-known semiempirical methods (parametric method 3 (PM3) and Zerner’s intermediate neglect of differential overlap (ZINDO)) coupled to the concepts of total and local density of states (LDOS). Our results indicate that regions presented by paclitaxel (Taxol®) as important for the biological activity can be traced out by the electronic features present in DBAC. These molecules differ only by a phenylisoserine side chain. Compared to paclitaxel, DBAC has a simpler structure in terms of molecular size and number of degrees of freedom (d.f.). This makes DBAC a good candidate for a preliminary investigation of the taxoid family. Our results question the importance of the oxetane group, which seems to be consistent with recent experimental data.
},
keywords = {Baccatin, Drug Design, Electronic Structure, Taxol, Taxotere, Theory of Electronic Indices},
pubstate = {published},
tppubtype = {article}
}
We performed a conformational and electronic analysis for 10-deacetylbaccatin-III (DBAC) using well-known semiempirical methods (parametric method 3 (PM3) and Zerner’s intermediate neglect of differential overlap (ZINDO)) coupled to the concepts of total and local density of states (LDOS). Our results indicate that regions presented by paclitaxel (Taxol®) as important for the biological activity can be traced out by the electronic features present in DBAC. These molecules differ only by a phenylisoserine side chain. Compared to paclitaxel, DBAC has a simpler structure in terms of molecular size and number of degrees of freedom (d.f.). This makes DBAC a good candidate for a preliminary investigation of the taxoid family. Our results question the importance of the oxetane group, which seems to be consistent with recent experimental data.
http://scholar.google.com/citations?hl=en&user=95SvbM8AAAAJ
