Marrero-Ponce Y.,Santa Clara University |
Marrero-Ponce Y.,University of Valencia |
Martinez E.R.,Santa Clara University |
Casanola-Martin G.M.,Santa Clara University |
And 4 more authors.
International Journal of Quantum Chemistry | Year: 2011
Bond-extended stochastic and nonstochastic bilinear indices are introduced in this article as novel bond-level molecular descriptors (MDs). These novel totals (whole-molecule) MDs are based on bilinear maps (forms) similar to use defined in linear algebra. The proposed nonstochastic indices try to match molecular structure provided by the molecular topology by using the kth Edge(Bond)-Adjacency Matrix (Ek, designed here as a nonstochastic E matrix). The stochastic parameters are computed by using the kth stochastic edge-adjacency matrix, ESk, as matrix operators of bilinear transformations. This new edge (bond)-adjacency relationship can be obtained directly from Ek and can be considered like a new matrix-transformation strategic to obtain new relations for a molecular graph. In both set of MDs, chemical information is codified by using different pair combinations of atomic weightings (in this case four atomic-labels: atomic mass, polarizability, van der Waals volume, and electronegativity). In addition, a local-fragment (bond-type) formalism was also developed. The kth bond-type bilinear indices are calculated by summing the kth bond bilinear indices of all bonds of the same bond type in the molecules. The new set of MDs can be easily and quickly calculated in our in house software TOMOCOMD-CARDD (topological molecular computational design computer-aided-rational-drug design). The reported application and utilization of these MDs for predictive capability correlations of structure with physicochemical and pharmacological properties are reviewed. Three benchmark datasets have been used to evaluate the QSPR/QSAR behavior of the new bond-level TOMOCOMD-CARDD MDs. We developed the QSPR models to describe several physicochemical properties of octane isomers (First Case) and, to analyze of the boiling point of 28 alkyl-alcohols (Second Case) and to examine of the specific rate constant (log k), the partition coefficient (log P), as well as the antibacterial activity of 34 derivatives of 2-furylethylenes (Third Case). For these three rounds, the quantitative models found are significant from a statistical point of view and permit a clear interpretation of the studied properties in terms of the structural features of molecules. A leave-one-out cross-validation procedure revealed that the regression models had a good predictability. The comparison with other approaches reveals good performance of the method proposed. Therefore, it is clearly demonstrated that this suitability is higher than that shown by other 2D/3D well-known sets of MDs. The approach described here appears to be a very promising structural invariant, useful for QSPR/QSAR studies and shown to provide an excellent alternative or guides for discovery and optimization of new lead compounds, reducing the time and cost of the traditional procedure. © 2009 Wiley Periodicals, Inc.
Garrido J.,Polytechnic Institute of Porto |
Garrido E.M.,Polytechnic Institute of Porto |
Journal of Chemical Education | Year: 2012
Antioxidants are additives largely used in industry for delaying, retarding, or preventing the development of oxidative deterioration. Propyl gallate (E310) is a phenolic antioxidant extensively used in the food, cosmetics, and pharmaceutical industries. A series of lab experiments have been developed to teach students about the importance and significance of antioxidants in industry. In the first laboratory, the antioxidant propyl gallate is obtained and the structure identified. Students become acquainted with laboratory techniques such as extraction, crystallization, and thin-layer chromatography. In the second laboratory, spectroscopic data (IR, 1H and 13C NMR) is acquired and interpreted. Students become familiar with the basic concepts of organic compound identification. In the third laboratory, the antioxidant activity of the synthesized additive and gallic acid is evaluated by DPPH (2,2-diphenyl-1-picrylhydrazyl) assay using trolox (6-hydroxy-2,5,7,8-tetramethylchroman- 2-carboxylic acid) as standard. Concepts such as free radical chemistry, preparation of analytical samples, calibration methods, and UV-vis spectrophotometry, are reviewed. This series of experiments can also be used to explore the effect of substituents on radical stability because structurally related compounds were found to have qualitatively different antioxidant profiles. Copyright © 2011 American Chemical Society and Division of Chemical Education, Inc.
Costa Lima S.,University of Porto |
Rodrigues V.,University of Porto |
Garrido J.,CIQUP |
Garrido J.,Polytechnic Institute of Porto |
And 3 more authors.
International Journal of Antimicrobial Agents | Year: 2012
Bisnaphthalimidopropyl (BNIP) derivatives have recently been shown to have potential as antileishmanial agents. However, these compounds have some drawbacks, including their low aqueous solubility and some toxic effects. In this study, we designed a drug delivery system for enhanced delivery of BNIP derivative compounds whilst reducing adverse toxic effects, and hence increasing their biological efficacy. A coated drug delivery system based on polymeric nanoparticles of pegylated poly(lactic acid) (PLA), a biodegradable polymer, was successfully achieved. The pegylated PLA nanoformulations loaded with BNIP derivatives were evaluated in an in vitro model of intracellular amastigotes in murine J774 and human THP-1 cells for visceral leishmaniasis using luciferase-expressing Leishmania infantum parasites. Pegylation of PLA nanoparticles significantly reduced the capacity of empty nanoparticles in inhibiting intracellular parasite growth. The BNIP derivatives BNIPDadec and BNIPDaoct exhibited EC 50 values (concentration of compound necessary to decrease cell viability to 50% of the untreated control) of ca. 4.5 μM for THP-1 and J774 cells and ca. 9.0 μM for mouse bone marrow-derived macrophages. Nanoparticle encapsulation of the BNIP derivative compounds decreased their toxicity towards macrophages by ≥10-fold as evaluated by the MTT assay. The antileishmanial activity of free BNIPDadec was 1.02 ± 0.41 μM and 0.73 ± 0.06 μM for THP-1 and J774 macrophages, respectively. Pegylation of PLA nanoparticles loaded with BNIPDadec resulted in EC 50 values of 1.43 ± 0.63 μM and 1.79 ± 0.77 μM for THP-1 and J774 macrophages, respectively. A similar trend was observed for free BNIPDaoct and pegylated BNIPDaoct PLA nanoparticles (2.43 ± 0.19 μM and 1.23 ± 0.40 μM for THP-1 macrophages and 1.36 ± 0.17 μM and 1.52 ± 0.57 μM for J774 macrophages). The nanoformulations were more efficient in reducing parasitic growth inside human macrophages than in murine cells, suggesting host cell-dependent metabolism. © 2012 Elsevier B.V. and the International Society of Chemotherapy.
Gomes L.R.,REQUIMTE |
Low J.N.,University of Aberdeen |
Borges F.,CIQUP |
Acta Crystallographica Section C: Crystal Structure Communications | Year: 2013
The title compound, C17H13NO4, crystallizes in two polymorphic forms, each with two mol ecules in the asymmetric unit and in the monoclinic space group P21/c. All of the mol ecules have intra molecular hydrogen bonds involving the amide group. The amide N atoms act as donors to the carbonyl group of the pyrone and also to the meth oxy group of the benzene ring. The carbonyl O atom of the amide group acts as an acceptor of the β and β′ C atoms belonging to the aromatic rings. These intra molecular hydrogen bonds have a profound effect on the mol ecular conformation. In one polymorph, the mol ecules in the asymmetric unit are linked to form dimers by weak C - H⋯O inter actions. In the other, the mol ecules in the asymmetric unit are linked by a single weak C - H⋯O hydrogen bond. Two of these units are linked to form centrosymmetric tetra mers by a second weak C - H⋯O inter action. Further inter actions of this type link the mol ecules into chains, so forming a three-dimensional network. These inter actions in both polymorphs are supplemented by π-π inter actions between the chromone rings and between the chromone and meth oxy phenyl rings. © 2013 International Union of Crystallography.