2014
Flavio, Ballante
Application of Medicinal Chemistry Methods on Different Classes of Drugs PhD Thesis
Sapienza University of Rome, 2014.
Abstract | Links | BibTeX | Tags: 3-D QSAutogrid/R, 3D QSAR, Biochemistry, BSAO, Chemoinformatics, Chemometrics, COMBINEr, CoMFA, DABO, DockAccessor, Docking Assessment, HCV NS5B, HDAC, HIV-1, HIV-RT, HSP90, HUVEC, Ligand-Based Design, Molecular Docking, Molecular Modeling, MPGRS, NNRTIs, Opioid-Receptor Antagonists, Organic Chemistry, Pharmacophoric Model, PLS, Tuberculosis, VEGFR-2, Virtual Screening
@phdthesis{Ballante2014b,
title = {Application of Medicinal Chemistry Methods on Different Classes of Drugs},
author = { Ballante Flavio},
editor = {PADIS},
url = {http://hdl.handle.net/11573/918780 },
year = {2014},
date = {2014-01-27},
address = {Department of Chemistry and Tecnology of Drugs},
school = {Sapienza University of Rome},
abstract = {The present doctoral thesis is the result of the work carried out during the three years of my PhD scholarship at the Rome Center for Molecular Design laboratory (RCMD, Department of Chemistry and Drug Technologies, Sapienza University of Rome), under the supervision of Prof. Rino Ragno. The research activity was focused mainly on the design, optimization and application of computational strategies to derive quantitative structure-activity relationships (QSAR, 3-D QSAR, and COMBINE) on different molecular classes of current interest, such as: opioid receptor antagonists (OPAs), Hepatitis C Virus NS5B-Polymerase Inhibitors (NS5B-NNIs), Hystone Deacetylase Inhibitors (HDACIs), Anti- tubercular agents, vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors, HSP90 inhibitors, HIV-1 reverse transcriptase inhibitors (NNRTIs), Bovine Serum Amine Oxidase (BSAO) substrates, etc... Moreover two research periods abroad were performed: the first framed in a LLP Erasmus program collaboration, was conducted for six months at the Laboratoire d'Ingénierie et Moléculaire Pharmacologique Biochimie (LIMBP) of the Université de Lorraine Metz (France), directed by Prof. Gilbert Kirsch, and characterized by the application of organic synthesis to obtain new thienopyrimidinone derivatives as potential inhibitors of vascular endothelial growth factor receptor-2 (VEGFR-2); the second took place, for three months, at the Department of Biochemistry and Molecular Biophysics in Washington University School of Medicine in Saint Louis (MO, USA), under the supervision of Prof. Garland R. Marshall, investigating the activity profile of new Histone Deacetylases (HDACs) inhibitors by the application of the Mobility Shift Assay Technology. Main purpose of this doctoral thesis is to highlight the activities carried out in the different research projects, the applied methodologies and the obtained results. The text starts describing those studies whose results were published in scientific journals (chapters I-VI): the author decided to omit some procedural details, completely reported in the published papers, that would make the text too long, tedious and redundant; therefore readers who want to delve these aspects can also refer to Chapter XII in which is possible to read the original papers; on the contrary for studies that have not yet been published, as those characterizing the Chapters VII and VIII, discussion is adequately detailed. Chapters IX and X report the scientific activities carried out in France and in USA respectively; Chapter XI summarizes all the scientific activities accomplished during the entire PhD course, whereas Chapter XII, as mentioned, contains the published articles.},
keywords = {3-D QSAutogrid/R, 3D QSAR, Biochemistry, BSAO, Chemoinformatics, Chemometrics, COMBINEr, CoMFA, DABO, DockAccessor, Docking Assessment, HCV NS5B, HDAC, HIV-1, HIV-RT, HSP90, HUVEC, Ligand-Based Design, Molecular Docking, Molecular Modeling, MPGRS, NNRTIs, Opioid-Receptor Antagonists, Organic Chemistry, Pharmacophoric Model, PLS, Tuberculosis, VEGFR-2, Virtual Screening},
pubstate = {published},
tppubtype = {phdthesis}
}
2013
Laura, Friggeri; Flavio, Ballante; Rino, Ragno; Ira, Musmuca; Daniela, De Vita; Fabrizio, Manetti; Mariangela, Biava; Luigi, Scipione; Roberto, Di Santo; Roberta, Costi; Marta, Feroci; Silvano, Tortorella
In: Journal of Chemical Information and Modeling, 53 (6), pp. 1463-1474, 2013.
Abstract | Links | BibTeX | Tags: 3-D QSAutogrid/R, 3D QSAR, Ligand-Based Design, MPGRS, Organic Chemistry, Pharmacophoric Model, PLS, Tuberculosis
@article{Friggeri2013,
title = {Pharmacophore assessment through 3-D QSAR: Evaluation of the predictive ability on new derivatives by the application on a series of antitubercular agents},
author = { Friggeri Laura and Ballante Flavio and Ragno Rino and Musmuca Ira and De Vita Daniela and Manetti Fabrizio and Biava Mariangela and Scipione Luigi and Di Santo Roberto and Costi Roberta and Feroci Marta and Tortorella Silvano},
editor = {American Chemical Society},
url = {http://pubs.acs.org/doi/abs/10.1021/ci400132q},
doi = {10.1021/ci400132q},
year = {2013},
date = {2013-05-17},
journal = {Journal of Chemical Information and Modeling},
volume = {53},
number = {6},
pages = {1463-1474},
abstract = {Pharmacophoric mapping is a useful procedure to frame, especially when crystallographic receptor structures are unavailable as in ligand-based studies, the hypothetical site of interaction. In this study, 71 pyrrole derivatives active against M. tuberculosis were used to derive through a recent new 3-D QSAR protocol, 3-D QSAutogrid/R, several predictive 3-D QSAR models on compounds aligned by a previously reported pharmacophoric application. A final multiprobe (MP) 3-D QSAR model was then obtained configuring itself as a tool to derive pharmacophoric quantitative models. To stress the applicability of the described models, an external test set of unrelated and newly synthesized series of R-4-amino-3-isoxazolidinone derivatives found to be active at micromolar level against M. tuberculosis was used, and the predicted bioactivities were in good agreement with the experimental values. The 3-D QSAutogrid/R procedure proved to be able to correlate by a single multi-informative scenario the different activity molecular profiles thus confirming its usefulness in the rational drug design approach.},
keywords = {3-D QSAutogrid/R, 3D QSAR, Ligand-Based Design, MPGRS, Organic Chemistry, Pharmacophoric Model, PLS, Tuberculosis},
pubstate = {published},
tppubtype = {article}
}