2017
Ballante, Flavio; Reddy, D. Rajasekhar; Zhou, Nancy J.; Marshall, Garland R.
In: Bioorganic & Medicinal Chemistry, 2017.
Links | BibTeX | Tags: 3D QSAR, Biochemistry, COMBINEr, Molecular Docking, Molecular Modeling, Organic Chemistry, PLS, Schistosoma mansoni, Virtual Screening
@article{Ballante2017,
title = {Structural Insights of SmKDAC8 Inhibitors: Targeting Schistosoma Epigenetics Through a Combined Structure-Based 3D QSAR, in vitro and Synthesis Strategy},
author = {Flavio Ballante and D. Rajasekhar Reddy and Nancy J. Zhou and Garland R. Marshall},
editor = {Elsevier},
url = {http://www.sciencedirect.com/science/article/pii/S0968089616314134},
year = {2017},
date = {2017-02-13},
journal = {Bioorganic & Medicinal Chemistry},
keywords = {3D QSAR, Biochemistry, COMBINEr, Molecular Docking, Molecular Modeling, Organic Chemistry, PLS, Schistosoma mansoni, Virtual Screening},
pubstate = {published},
tppubtype = {article}
}
2014
Dante, Rotili; Domenico, Tarantino; Maxim B, Nawrozkij; Alexandre S, Babushkin; Giorgia, Botta; Biagina, Marrocco; Roberto, Cirilli; Sergio, Menta; Roger, Badia; Emmanuele, Crespan; Flavio, Ballante; Rino, Ragno; José A, Esté; Giovanni, Maga; Antonello, Mai
In: Journal of Medicinal Chemistry, 57 (12), pp. 5212-5225, 2014.
Abstract | Links | BibTeX | Tags: Biochemistry, COMBINEr, DABO, HIV-1, HIV-RT, Molecular Docking, Molecular Modeling, NNRTIs, Organic Chemistry, PLS
@article{Rotili2014,
title = {Exploring the Role of 2 ‑ Chloro-6- fluoro Substitution in 2 ‑ Alkylthio-6- benzyl-5-alkylpyrimidin-4(3 H ) ‑ ones: Effects in HIV-1-Infected Cells and in HIV ‑ 1 Reverse Transcriptase Enzymes},
author = {Rotili Dante and Tarantino Domenico and Maxim B, Nawrozkij and Alexandre S, Babushkin and Botta Giorgia and Marrocco Biagina and Cirilli Roberto and Menta Sergio and Badia Roger and Crespan Emmanuele and Ballante Flavio and Ragno Rino and José A, Esté and Maga Giovanni and Mai Antonello},
editor = {American Chemical Society},
url = {http://pubs.acs.org/doi/abs/10.1021/jm500284x},
doi = {10.1021/jm500284x},
year = {2014},
date = {2014-06-16},
journal = {Journal of Medicinal Chemistry},
volume = {57},
number = {12},
pages = {5212-5225},
abstract = {A comparison of the effects of the 6-(2-chloro-6-fluorobenzyl)-2-(alkylthio)pyrimidin-4(3H)-ones (2-Cl-6-F-S-DABOs) 7–12 and the related 6-(2,6-difluorobenzyl) counterparts 13–15 in HIV-1 infected cells and in the HIV-1 reverse transcriptase (RT) assays is here described. The new 2-Cl-6-F-S-DABOs showed up to picomolar activity against wt HIV-1. Against clinically relevant HIV-1 mutants and in enzyme assays, the simultaneous C5(methyl)/C6(methyl/ethyl) substitution in the 2-Cl-6-F- and 2,6-F2-benzyl series furnished compounds with the highest, wide-spectrum inhibitory activity against HIV-1. Three representative 2-Cl-6-F-S-DABOs carrying two (9c, 10c) or one (10a) stereogenic centers were resolved into their individual stereoisomers and showed a significant diastereo- and enantioselectivity in HIV-1 inhibition, the highest antiviral activity well correlating with the R absolute configuration to the stereogenic center of the C6-benzylic position in both cellular and enzymatic tests. Application of previously reported COMBINEr protocol on 9c and 10c confirmed the influence of the stereogenic centers on their binding modes in the HIV-1 RT.},
keywords = {Biochemistry, COMBINEr, DABO, HIV-1, HIV-RT, Molecular Docking, Molecular Modeling, NNRTIs, Organic Chemistry, PLS},
pubstate = {published},
tppubtype = {article}
}
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}
}
2012
Flavio, Ballante; Ira, Musmuca; Marshall, Garland R; Rino, Ragno
Comprehensive model of wild-type and mutant HIV-1 reverse transciptases Journal Article
In: Journal of Computer-Aided Molecular Design, 26 (8), pp. 907-919, 2012.
Abstract | Links | BibTeX | Tags: 3D QSAR, COMBINEr, DABO, HIV-1, HIV-RT, PLS
@article{Ballante2012b,
title = {Comprehensive model of wild-type and mutant HIV-1 reverse transciptases},
author = { Ballante Flavio and Musmuca Ira and Garland R Marshall and Ragno Rino},
editor = {Springer Netherlands},
url = {http://link.springer.com/article/10.1007/s10822-012-9586-6#},
doi = {10.1007/s10822-012-9586-6},
year = {2012},
date = {2012-07-26},
urldate = {2012-07-26},
journal = {Journal of Computer-Aided Molecular Design},
volume = {26},
number = {8},
pages = {907-919},
abstract = {An enhanced version of COMBINE that uses both ligand-based and structure-based alignment of ligands has been used to build a comprehensive 3-D QSAR model of wild-type HIV-1 reverse transcriptase and drug-resistant mutants. The COMBINEr model focused on 7 different RT enzymes complexed with just two HIV-RT inhibitors, niverapine (NVP) and efavirenz (EFV); therefore, 14 inhibitor/enzyme complexes comprised the training set. An external test set of chiral 2-(alkyl/aryl)amino-6-benzylpyrimidin-4(3H)-ones (DABOs) was used to test predictability. The COMBINEr model MC4, although developed using only two inhibitors, predicted the experimental activities of the test set with an acceptable average absolute error of prediction (0.89 pK i). Most notably, the model was able to correctly predict the right eudismic ratio for two R/S pairs of DABO derivatives. The enhanced COMBINEr approach was developed using only software freely available to academics.},
keywords = {3D QSAR, COMBINEr, DABO, HIV-1, HIV-RT, PLS},
pubstate = {published},
tppubtype = {article}
}
Laura, Silvestri; Flavio, Ballante; Antonello, Mai; Garland R, Marshall; Rino, Ragno
Histone Deacetylase Inhibitors: Structure-Based Modeling and Isoform-Selectivity Prediction Journal Article
In: Journal of Chemical Information and Modeling, 52 (8), pp. 2215-2235, 2012.
Abstract | Links | BibTeX | Tags: 3D QSAR, COMBINEr, HDAC, Molecular Docking, Molecular Modeling, PLS
@article{Silvestri2012,
title = {Histone Deacetylase Inhibitors: Structure-Based Modeling and Isoform-Selectivity Prediction},
author = { Silvestri Laura and Ballante Flavio and Mai Antonello and Garland R, Marshall and Ragno Rino},
editor = {American Chemical Society},
url = {http://pubs.acs.org/doi/abs/10.1021/ci300160y},
doi = {10.1021/ci300160y},
year = {2012},
date = {2012-07-19},
journal = {Journal of Chemical Information and Modeling},
volume = { 52},
number = {8},
pages = {2215-2235},
abstract = {An enhanced version of comparative binding energy (COMBINE) analysis, named COMBINEr, based on both ligand-based and structure-based alignments has been used to build several 3-D QSAR models for the eleven human zinc-based histone deacetylases (HDACs). When faced with an abundance of data from diverse structure–activity sources, choosing the best paradigm for an integrative analysis is difficult. A common example from studies on enzyme–inhibitors is the abundance of crystal structures characterized by diverse ligands complexed with different enzyme isoforms. A novel comprehensive tool for data mining on such inhomogeneous set of structure–activity data was developed based on the original approach of Ortiz, Gago, and Wade, and applied to predict HDAC inhibitors’ isoform selectivity. The COMBINEr approach (apart from the AMBER programs) has been developed to use only software freely available to academics.},
keywords = {3D QSAR, COMBINEr, HDAC, Molecular Docking, Molecular Modeling, PLS},
pubstate = {published},
tppubtype = {article}
}
Dante, Rotili; Alberta, Samuele; Domenico, Tarantino; Rino, Ragno; Ira, Musmuca; Flavio, Ballante; Giorgia, Botta; Ludovica, Morera; Marco, Pierini; Roberto, Cirilli; Maxim B, Nawrozkij; Emmanuel, Gonzalez; Bonaventura, Clotet; Marino, Artico; José A, Esté; Giovanni, Maga; Antonello, Mai
2-(Alkyl/aryl) amino-6-benzylpyrimidin-4 (3H)-ones as inhibitors of wild-type and mutant HIV-1: enantioselectivity studies Journal Article
In: Journal of Medicinal Chemistry, 55 (7), pp. 3558-3562, 2012.
Abstract | Links | BibTeX | Tags: Biochemistry, COMBINEr, DABO, HIV-1, Molecular Docking, Molecular Modeling, NNRTIs, Organic Chemistry
@article{Rotili2012,
title = {2-(Alkyl/aryl) amino-6-benzylpyrimidin-4 (3H)-ones as inhibitors of wild-type and mutant HIV-1: enantioselectivity studies},
author = { Rotili Dante and Samuele Alberta and Tarantino Domenico and Ragno Rino and Musmuca Ira and Ballante Flavio and Botta Giorgia and Morera Ludovica and Pierini Marco and Cirilli Roberto and Maxim B, Nawrozkij and Gonzalez Emmanuel and Clotet Bonaventura and Artico Marino and José A, Esté and Maga Giovanni and Mai Antonello},
editor = {American Chemical Society},
url = {https://pubs.acs.org/doi/10.1021/jm201308v},
doi = {10.1021/jm201308v},
year = {2012},
date = {2012-03-26},
journal = {Journal of Medicinal Chemistry},
volume = {55},
number = {7},
pages = {3558-3562},
abstract = {The single enantiomers of two pyrimidine-based HIV-1 non-nucleoside reverse transcriptase inhibitors, 1 (MC1501) and 2 (MC2082), were tested in both cellular and enzyme assays. In general, the R forms were more potent than their S counterparts and racemates and (R)-2 was more efficient than (R)-1 and the reference compounds, with some exceptions. Interestingly, (R)-2 displayed a faster binding to K103N RT with respect to WT RT, while (R)-1 showed the opposite behavior.},
keywords = {Biochemistry, COMBINEr, DABO, HIV-1, Molecular Docking, Molecular Modeling, NNRTIs, Organic Chemistry},
pubstate = {published},
tppubtype = {article}
}