Francisco M. Garibotto
National Scientific and Technical Research Council
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Featured researches published by Francisco M. Garibotto.
Bioorganic & Medicinal Chemistry | 2010
Francisco M. Garibotto; Adriana D. Garro; Marcelo F. Masman; A.M. Rodrı́guez; Paul G.M. Luiten; Marcela Raimondi; Susana Zacchino; Csaba Somlai; Botond Penke; Ricardo D. Enriz
The synthesis, in vitro evaluation, and conformational study of a new series of small-size peptides acting as antifungal agents are reported. In a first step of our study we performed a conformational analysis using Molecular Mechanics calculations. The electronic study was carried out using Molecular electrostatic potentials (MEPs) obtained from RHF/6-31G calculations. On the basis of the theoretical predictions three small-size peptides, RQWKKWWQWRR-NH(2), RQIRRWWQWRR-NH(2), and RQIRRWWQW-NH(2) were synthesized and tested. These peptides displayed a significant antifungal activity against human pathogenic strains including Candida albicans and Cryptococcus neoformans. Our experimental and theoretical results allow the identification of a topographical template which can serve as a guide for the design of new compounds with antifungal properties for potential therapeutic applications against these pathogenic fungi.
Molecules | 2013
Marcos Derita; Iván Montenegro; Francisco M. Garibotto; Ricardo D. Enriz; Mauricio Cuellar Fritis; Susana Zacchino
Seventeen drimanes including polygodial (1), isopolygodial (2), drimenol (3) and confertifolin (4) obtained from natural sources and the semi-synthetic derivatives 5–17 obtained from 1–3, were evaluated in vitro for antifungal properties against a unique panel of fungi with standardized procedures by using two end-points, MIC100 and MIC50. A SAR analysis of the whole series, supported by conformational and electronic studies, allowed us to show that the Δ7,8 -double bond would be one of the key structural features related to the antifungal activity. The MEPs obtained for active compounds exhibit a clear negative minimum value (deep red zone) in the vicinity of the Δ7,8 -double bond, which is not present in the inactive ones. Apart of this negative zone, a positive region (deep blue) appears in 1, which is not observed either in its epimer 2 nor in the rest of the active compounds. The LogP of active compounds varies between 2.33 and 3.84, but differences in MICs are not correlated with concomitant variations in LogP values.
European Journal of Medicinal Chemistry | 2011
Francisco M. Garibotto; Adriana D. Garro; Ana Rodriguez; Marcela Raimondi; Susana Zacchino; András Perczel; Csaba Somlai; Botond Penke; Ricardo D. Enriz
The synthesis, in vitro evaluation, and conformational study of penetratin analogues acting as antifungal agents are reported. Different peptides structurally related with penetratin were evaluated. Analogues of penetratin rich in Arg, Lys and Trp amino acids were tested. In addition, HFRWRQIKIWFQNRRM[O]KWKK-NH(2), a synthetic 20 amino acid peptide was also evaluated. These penetratin analogues displayed antifungal activity against human pathogenic strains including Candida albicans and Cryptococcus neoformans. In contrast, Tat peptide, a well-known cell penetrating peptide, did not show a significant antifungal activity against fungus tested here. We also performed a conformational study by means experimental and theoretical approaches (CD spectroscopic measurements and MD simulations). The electronic structure analysis was carried out from Molecular Electrostatic Potentials (MEP) obtained by using RHF/6-31G ab initio calculations. Our experimental and theoretical results permitted us to identify a topographical template which may provide a guide for the design of new peptides with antifungal effects.
Medicinal Chemistry Research | 2017
Juan C. Garro Martinez; Matias F. Andrada; Esteban G. Vega-Hissi; Francisco M. Garibotto; Manuel Nogueras; Ricaurte Rodríguez; Justo Cobo; Ricardo D. Enriz; Mario R. Estrada
In this work, we study the structure–activity relationship of a series of Dihydrofolate reductase inhibitors by two-dimensional quantitative activity–structure relationship and three-dimensional quantitative activity–structure relationship techniques. The two-dimensional quantitative activity–structure relationship models were developed by using two different types of topological molecular descriptors, PaDEL and Dragon descriptors. The models showed an excellent predictive power, R2train = 0.916 and R2val = 0.806 for the PaDEL, and R2train = 0.952 and R2val = 0.963 for those obtained with Dragon descriptors. Simple molecular descriptors as maxHCsats, IC3, SPI, SIC2, and GATS5p were adequate to obtain predictive models. The three-dimensional quantitative activity–structure relationship was performed through three variable selected approaches, Partial Linear Square (PLS), Fractional Factorial Design (FFD) and Uninformative Variable Elimination-Partial Linear Square (UVE-PLS) using the Open3DQSAR software. All the 2D and 3D models were validated using two compounds (number 24 and 25), which were synthesized and presented here for the first time. Their biological activities were correctly predicted by all the quantitative activity–structure relationship models. Finally, we proposed three compounds (26, 27, and 28), which showed a high predicted Dihydrofolate reductase inhibitory activity. Molecular docking study suggested that compounds bind to receptor similarly to the most active inhibitors.
Molecular Informatics | 2015
Emilio L. Angelina; Sebastián A. Andujar; Laura Moreno; Francisco M. Garibotto; Javier Párraga; Nélida M. Peruchena; Nuria Cabedo; Margarita Villecco; Diego Cortes; Ricardo D. Enriz
We synthesized and tested 3‐chlorotyramine as a ligand of the D2 dopamine receptor. This compound displayed a similar affinity by this receptor to that previously reported for dopamine. In order to understand further the experimental results we performed a molecular modeling study of 3‐chlorotyramine and structurally related compounds. By combining molecular dynamics simulations with semiempirical (PM6), ab initio and density functional theory calculations, a simple and generally applicable procedure to evaluate the binding energies of these ligands interacting with the D2 dopamine receptors is reported here. These results provided a clear picture of the binding interactions of these compounds from both structural and energetic view points. A reduced model for the binding pocket was used. This approach allowed us to perform more accurate quantum mechanical calculations as well as to obtain a detailed electronic analysis using the Quantum Theory of Atoms in Molecules (QTAIM) technique. Molecular aspects of the binding interactions between ligands and the D2 dopamine receptor are discussed in detail. A good correlation between the relative binding energies obtained from theoretical calculations and experimental IC50 values was obtained. These results allowed us to predict that 3‐chlorotyramine possesses a significant affinity by the D2‐DR. Our theoretical predictions were experimentally corroborated when we synthesized and tested 3‐chlorotyramine which displayed a similar affinity by the D2‐DR to that reported for DA.
Molecules | 2018
Juan G. Dolab; Beatriz Lima; Ewelina Spaczynska; Jiri Kos; Natividad Cano; Gabriela Egly Feresin; Alejandro Tapia; Francisco M. Garibotto; Elisa Petenatti; Monica Olivella; Robert Musiol; Josef Jampilek; Ricardo D. Enriz
Annona emarginata (Schltdl.) H. Rainer, commonly known as “arachichú”, “araticú”, “aratigú”, and “yerba mora”, is a plant that grows in Argentina. Infusions and decoctions are used in folk medicine as a gargle against throat pain and for calming toothache; another way to use the plant for these purposes is chewing its leaves. Extracts from bark, flowers, leaves, and fruits from A. emarginata were subjected to antibacterial assays against a panel of Gram (+) and Gram (−) pathogenic bacteria according to Clinical and Laboratory Standards Institute protocols. Extracts from the stem bark and leaves showed moderate activity against the bacteria tested with values between 250–1000 µg/mL. Regarding flower extracts, less polar extracts (hexane, dichloromethane) showed very strong antibacterial activity against methicillin-sensitive Staphylococcus aureus ATCC 25923 and methicillin-resistant S. aureus ATCC 43300 with values between 16–125 µg/mL. Additionally, hexane extract showed activity against Klebsiella pneumoniae (MIC = 250 µg/mL). The global methanolic extract of the fruits (MeOHGEF) was also active against the three strains mentioned above, with MICs values 250–500 µg/mL. Bioassay-guided fractionation of MeOHGEF led to the isolation of a new main compound—(R)-2-(4-methylcyclohex-3-en-1-yl)propan-2-yl (E)-3-(4-hydroxyphenyl)acrylate (1). The structure and relative configurations have been determined by means of 1D and 2D NMR techniques, including COSY, HMQC, HMBC, and NOESY correlations. Compound 1 showed strong antimicrobial activity against all Gram (+) species tested (MICs = 3.12–6.25 µg/mL). In addition, the synthesis and antibacterial activity of some compounds structurally related to compound 1 (including four new compounds) are reported. A SAR study for these compounds was performed based on the results obtained by using molecular calculations.
Bioorganic & Medicinal Chemistry | 2007
Maximiliano Sortino; Paula Delgado; Sabina Juárez; Jairo Quiroga; Rodrigo Abonia; Braulio Insuasty; Manuel Nogueras; Laura Rodero; Francisco M. Garibotto; Ricardo D. Enriz; Susana Zacchino
Journal of Agricultural and Food Chemistry | 2007
Fabricio R. Bisogno; Laura Mascoti; Cecilia Sanchez; Francisco M. Garibotto; Fernando Giannini; Marcela Kurina-Sanz; Ricardo D. Enriz
Computational and Theoretical Chemistry | 2016
Exequiel Ernesto Barrera Guisasola; Lucas J. Gutierrez; Rodrigo E. Salcedo; Francisco M. Garibotto; Sebastián A. Andujar; Ricardo D. Enriz; Ana M. Rodríguez
Letters in Drug Design & Discovery | 2011
Adriana D. Garro; Francisco M. Garibotto; Ana Rodriguez; Marcela Raimondi; Susana Zacchino; András Perczel; Csaba Somlai; Botond Penke; Ricardo D. Enriz