Luis E. Bruno‐Blanch

Universidad Nacional de La Plata

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Alan Talevi

Universidad Nacional de La Plata

Eduardo A. Castro

Universidad Nacional de La Plata

Luciana Gavernet

Universidad Nacional de La Plata

Andrea Enrique

Consejo Nacional de Investigaciones Científicas y Técnicas

Carolina L. Bellera

Centro Científico Tecnológico - La Plata

Mauricio E. Di Ianni

Universidad Nacional de La Plata

Guillermina Estiú

University of Notre Dame

Melisa E. Gantner

Universidad Nacional de La Plata

Valentina Pastore

University of Buenos Aires

Silvina M. Tasso

Universidad Nacional de La Plata

Cooperative Institutions

Universidad Nacional de La Plata

Consejo Nacional de Investigaciones Científicas y Técnicas

University of Buenos Aires

Centro Científico Tecnológico - La Plata

Centro Científico Tecnológico - San Juan

Centro de Investigación y Desarrollo

Exact Sciences (United States)

University of Notre Dame

Instituto de Química y Fisicoquímica Biológicas

Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Computer-Aided Identification of Anticonvulsant Effect of Natural Nonnutritive Sweeteners Stevioside and Rebaudioside A

Assay and Drug Development Technologies (2015)

Mauricio E. Di Ianni Mara E. del Valle Andrea Enrique M.A Rosella Fiorella Bruno

Steviol glycosides are natural constituents of Stevia rebaudiana (Bert.) Bert. (Asteraceae) that have recently gained worldwide approval as nonnutritive sweeteners by the Joint Food and Agriculture Organization/World Organization Expert Committee on Food Additives. Cheminformatic tools suggested that the aglycone steviol and several of its phase I metabolites were predicted as potential anticonvulsant agents effective in the seizure animal model maximal electroshock seizure (MES) test. Thus, aqueous infusion from S. rebaudiana was tested in the MES test (mice, intraperitoneal administration), confirming dose-dependent anticonvulsant effect. Afterward, isolated stevioside and rebaudioside A were tested in the MES test, with positive results. Though drug repositioning most often focuses on known therapeutics, this article illustrates the possibilities of this strategy to find new functionalities and therapeutic indications for food constituents and natural products.

Stevia rebaudiana

Rebaudioside A

Steviol

Aglycone

Food additive

Stevia

10.1089/adt.2015.29010.meddrrr

Cite

Citations (12)

Discovering New Antiepileptic Drugs Addressing the Transporter Hypothesis of Refractory Epilepsy: Ligand-Based Approximations

Methods in pharmacology and toxicology (2016)

Manuel Couyoupetrou Mauricio Di Ianni Melisa E. Gantner Guido Pesce Roxana N. Peroni

About one third of the epileptic patients cannot control their symptoms with antiepileptic drugs, despite the introduction of more than 15 novel therapeutic agents to the market since 1990. The most studied hypothesis to explain the phenomenon of drug resistance in epilepsy maintains that it might be related to regional overactivity of efflux transporters from the ATP-binding cassette (ABC) superfamily at the blood–brain barrier and/or the epileptic foci. Here, we review scientific evidence supporting the transporter hypothesis along with its limitations. We also cover some technical aspects of computational and experimental approaches used for the early detection of substrates of such efflux systems.

Refractory (planetary science)

10.1007/978-1-4939-6355-3_14

Cite

Citations (2)

Carbamazepine-loaded solid lipid nanoparticles and nanostructured lipid carriers: Physicochemical characterization and in vitro/in vivo evaluation

Colloids and Surfaces B Biointerfaces (2018)

Sebastián Scioli Montoto María Laura Sbaraglini Alan Talevi Manuel Couyoupetrou M. Di Ianni

Solid lipid nanoparticle

Nanocarriers

Sonication

10.1016/j.colsurfb.2018.03.052

Cite

Citations (92)

Docking Applied to the Study of Inhibitors of c-Met Kinase

ISRN Physical Chemistry (2011)

Luciana Gavernet Pablo H. Palestro Luis E. Bruno‐Blanch

Quinoxaline derivatives were studied as inhibitors of c-Met kinase, a receptor associated with high tumor grade and poor prognosis in a number of human cancers. In this paper we used docking methodologies to predict the binding conformation of a set of quinoxalines and to explain the differences of biological activities previously reported.

Docking (animal)

Quinoxaline

10.5402/2012/391897

Cite

Citations (4)

A Combined Virtual Screening 2D and 3D QSAR Methodology for the Selection of New Anticonvulsant Candidates from a Natural Product Library

QSAR & Combinatorial Science (2008)

Luciana Gavernet Alan Talevi Eduardo Castro Luis E. Bruno‐Blanch

Abstract A virtual screening methodology combining a discriminant function (df) based on Dragon 2D‐descriptors, general ADME filters, and a pharmacophore identified through superposition of rigid analogs was applied in order to identify new anticonvulsant agents among 10 903 natural products. Fifty‐six compounds were selected from the application of this df, Lipinski's rule‐of‐five and other criteria for prediction of oral bioavailability, and the optimal value of log P for a compound to diffuse passively through the blood–brain barrier. Seven of these compounds were removed because they did not belong to descriptor space defined by the training set. The remaining 49 compounds were fitted to the pharmacophore structural constrains, selecting 7 structures with RMS distance value below 0.2. Systematic conformational analysis was performed to find the global minimum conformation, using the PM3 base included in Hyperchem 6.03. The global minimum conformations were further refined at a 6‐31G** level with Gaussian 03. Restricted optimization was then performed to determine the energy difference between the energy minimum conformation and the active conformation defined by the pharmacophore, retaining those structures whose energy differences were below 7 kcal/mol. Four new potential anticonvulsants which fulfill the df and the pharmacophore requisites were selected. One of these structures, 2‐(4,6‐dimethyl‐1‐benzofuran‐3‐yl)acetic acid, was acquired and assayed in the MES and Rotorod tests, confirming anticonvulsant activity in mice at 30 and 100 mg/kg (0.5 and 4 h, i.p.) and absence of neurotoxicity at the tested doses.

10.1002/qsar.200730055

Cite

Citations (22)

ChemInform Abstract: Synthesis and Pharmacological Evaluation of Prodrugs of Valproic Acid.

ChemInform (2000)

Nicholas Bodor S. Chin Moon Luis E. Bruno‐Blanch

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Valproic Acid

10.1002/chin.200031243

Cite

Citations (1)

Theoretical approach to the pharmacophoric pattern of GABAB analogs

International Journal of Quantum Chemistry (1998)

M. L. Lorenzini Luis E. Bruno‐Blanch G. L. Esti�

In order to determine the structural requirements that are important for GABAB binding affinity, a quantum-chemical-based conformational study has been performed, followed by a similarity analysis which includes 12 GABAB analogs. Due to the flexibility of the structures, a semigrid GABAB analog [2RS-(5,5-dimethyl) morpholinyl-acetic acid] has been used as a template for the amonium moiety in order to help to identify the active conformation. Both in vacuo, and solvent-simulated calculations, for the physiological media modeled as water molecules, have been compared, for this analog, at ab initio (G94, 6-31+G(d,p)) and semiempirical (PM3) levels, respectively. On the basis of this comparison, the results of in vacuo PM3 calculations have been chosen for the similarity analysis. We have included, in the calculations, a group of molecules heterogeneous enough to become representative of the different families that can bind to the GABAB receptor site. Following their comparison we report the leading characteristics that can be related to their binding capability and define a pharmacophoric pattern for GABAB analogs. The latter is compared with the one previously found for the binding affinity at the GABAA receptor site. © 1998 John Wiley & Sons, Inc. Int J Quant Chem 70: 1195–1208, 1998

GABAB receptor

Moiety

Similarity (geometry)

10.1002/(sici)1097-461x(1998)70:6<1195::aid-qua9>3.0.co;2-v

Cite

Citations (10)

N,N′-Dicyclohexylsulfamide and N,N′-diphenethylsulfamide are anticonvulsant sulfamides with affinity for the benzodiazepine binding site of the GABAA receptor and anxiolytic activity in mice

Biochemical Pharmacology (2011)

Cristina Wasowski Luciana Gavernet Ivana Analía Barrios María L. Villalba Valentina Pastore

Flumazenil

Elevated plus maze

10.1016/j.bcp.2011.10.015

Cite

Citations (17)

A successful virtual screening application: prediction of anticonvulsant activity in MES test of widely used pharmaceutical and food preservatives methylparaben and propylparaben

Journal of Computer-Aided Molecular Design (2007)

Alan Talevi Carolina L. Bellera Eduardo A. Castro Luis E. Bruno‐Blanch

Propylparaben

Paraben

Pharmaceutics

10.1007/s10822-007-9136-9

Cite

Citations (38)

Integrated Application of Enhanced Replacement Method and Ensemble Learning for the Prediction of BCRP/ABCG2 Substrates

Current Bioinformatics (2015)

Melisa E. Gantner Lucas N. Alberca Andrew G. Mercader Luis E. Bruno‐Blanch Alan Talevi

Background: Breast Cancer Resistance Protein (BCRP or ABCG2) is a polyspecific effluxtransporter which belongs to the ATP-binding Cassette superfamily. Up-regulation of BCRP is associated to multi-drug resistance in a number of conditions, e.g. cancer and epilepsy. Recent proteomic studies show that high expression levels of BCRP are found in healthy human intestine and at the blood-brain barrier, limiting the absorption and brain distribution of its substrates. Therefore, the early recognition of BCRP substrates seems to be crucial in the early phase of drug discovery. Keywords: Breast Cancer Resistance Protein, ABC transporters, ABCG2, enhanced replacement method, ensemble learning, linear classifiers.

Abcg2

Limiting

10.2174/1574893611666151109193016

Cite

Citations (4)