Publications

Abstract Four N-(4-halophenyl)-4-oxo-4H-chromene-3-carboxamides (halo = F, Cl, Br and I), N-(4-fluorophenyl)-4-oxo-4H-chromene-3-carboxamide, C16H10FNO3, N-(4-chlorophenyl)-4-oxo-4H-chromene-3-carboxamide, C16H10ClNO3, N-(4-bromophenyl)-4-oxo-4H-chromene-3-carboxamide, C16H10BrNO3, N-(4-iodopheny1)-4-oxo-4H-chromene-3-carboxamide, C16H10INO3, have been structurally characterized. The molecules are essentially planar and each exhibits an anti conformation with respect to the C-N rotamer of the amide and a cis geometry with respect to the relative positions of the C-arom-C-arom bond of the chromone ring and the carbonyl group of the amide. The structures each exhibit an intramolecular hydrogen-bonding network comprising an N-H center dot center dot center dot O hydrogen bond between the amide N atom and the 0 atom of the carbonyl group of the pyrone ring, forming an S(6) ring, and a weak C-arom-H center dot center dot center dot O interaction with the O atom of the carbonyl group of the amide as acceptor, which forms another S(6) ring. All four compounds have the same supra molecular structure, consisting of R-2(2)(13) rings that are propagated along the a axis direction by unit translation. There is pi-pi stacking involving inversion related molecules in each structure.

Abstract The knowledge of the thermodynamic properties of heterocyclic compounds, particularly the corresponding enthalpies of formation in condensed and gaseous states, enables a better understanding of their chemical behavior and, consequently, leads to an important background for the future development of their practical applications. Following our particular interest along the last decade on the establishment of energetic and structural relationships for heterocycle compounds with one or two benzene rings fused to a five- or six-membered ring containing oxygen or sulfur heteroatoms, we review the thermochemical data for derivatives of the following main structures: benzoxazole/benzothiazole, dibenzofuran/dibenzothiophene, xanthene/thioxanthene, and phenoxazine/phenothiazine. The experimental results, obtained by calorimetric and effusion techniques, namely static and rotating bomb combustion calorimetry, vacuum sublimation/vaporization drop microcalorimetry, and Knudsen effusion methods, were used to derive reliable thermodynamic values for the compounds studied. A complementary analysis of computational results for these molecules is presented. The agreement between the calculated and the experimental gas-phase enthalpies of formation represents a reinforcement on the validation of the established predictive schemes, supporting their use for related compounds whose energetic study is not available.

Abstract The title compounds, 6-(2-hydroxybenzyl)-5H-thiazolo[3,2-a] pyrimidin-5-one, C13H8N2O3S, (1), and 6-(2-hydroxybenzyl)-3-methyl-5H-thiazolo[3,2-a] pyrimidin-5-one, C14H10N2O3S, (2), were synthesized when a chromone-3-carboxylic acid, activated with (benzotriazol-1-yloxy)tripyrrolidinylphosphonium hexafluoridophosphate (PyBOP), was reacted with a primary heteromamine. Instead of the expected amidation, the unusual title thiazolopyrimidine-5-one derivatives were obtained serendipitously and a mechanism of formation is proposed. Both compounds present an intramolecular O-H center dot center dot center dot O hydrogen bond, which generates an S(6) ring. The dihedral angles between the heterocyclic moiety and the 2-hydroxybenzoyl ring are 55.22 (5) and 46.83 (6)degrees for (1) and (2), respectively. In the crystals, the molecules are linked by weak C-H center dot center dot center dot O hydrogen bonds and pi-pi stacking interactions.

Abstract Tropical parasitic diseases, especially those produced by protozoan parasites, are a major public health problem in many countries, and their impact in the health burden is significant. Oxidative processes proved to be related to these diseases, being the antioxidant agents promising therapeutic solutions for them. Therefore, this review provides an overview of published manuscripts regarding both activities. In particular, the interest of the coumarin derivatives as antioxidant agents with application in parasitic diseases is discussed in this manuscript. The recent findings in this field are highlighted.

Abstract Vesicles based on mixed cationic and anionic surfactants (catanionic vesicles) offer a number of advantageous colloidal features over conventional lipid-based vesicles, namely spontaneity in formation, long-term stability, and easy modulation of size and charge. If biocompatibility is added through rational design of the chemical components, the potential for biorelated applications further emerges. Here, we report for the first time on two catanionic vesicle systems in which both ionic amphiphiles are derivatized from the same amino acid-serine-with the goal of enhancing aggregate biocompatibility. Phase behavior maps for a mixture with chain length symmetry, 12Ser/12-12Ser, and another with asymmetry, 16Ser/8-8Ser, are presented, for which regions of vesicles, micelles, and coexisting aggregates are identified. For the asymmetric mixture, detailed phase behavior and microstructure characterization have been carried out based on surface tension, light microscopy, cryo-SEM, cryo-TEM, and dynamic light scattering analysis. Vesicles are found with tunable mean size, pH, and zeta potential. Changes in aggregate shape with varying composition and the effect of preparation methods and aging on vesicle features and stability have been investigated in detail. The results are discussed in the light of self-assembly models and related catanionic systems reported before. A versatile system of robust vesicles is thus presented for potential applications.

Abstract Monoamine oxidase (MAO) generates reactive oxygen species (ROS), which cause neuronal cell death, causing neurodegeneration. Agents that are able to concurrently inhibit MAO and scavenge free radicals represent promising multifunctional neuroprotective agents that could be used to delay or slow the progression of neurodegenerative diseases. In this work, variously substituted 3-amidocoumarins are described that exert neuroprotection in vitro against hydrogen peroxide in rat cortical neurons, as well as antioxidant activity in a 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. Selective and reversible inhibitors of the MAO-B isoform were identified. Interestingly, in the case of the 3-benzamidocoumarins, substitution at position4 with a hydroxy group abolishes MAO-B activity, but the compounds remain active in the neuroprotection model. Further evaluation of 3-heteroarylamide derivatives indicates that it is the nature of the heterocycle that determines the neuroprotective effects. Evaluation in a parallel artificial membrane permeability assay (PAMPA) highlighted the need to further improve the blood-brain barrier permeability of this compound class. However, the compounds described herein adhere to Lipinskis rule of five, suggesting that this novel scaffold has desirable properties for the development of potential drug candidates.

Abstract Introduction: Chromones are one of the major classes of naturally occurring compounds. Their chemistry has been widely explored and extensively reviewed. The following review intends to give a broad overview of the patented chromones. Particular attention has been given to their synthesis, uses and applications in last 10 years.Areas covered: The authors provide an overview of the recent scientific reports describing the obtaining and study of new chromones. The review emphasizes the rationale behind natural sources, synthesis, biological activities and structure-activity relationships of the new chromone derivatives. The article is based on the literature published from 2005 to 2015 related to the development of this family of compounds. The patents presented in this review have been collected from multiple electronic databases including SciFinder, Espacenet and Mendeley.Expert opinion: Although a great number of chromones have been published in bibliographic sources in the last years, there is little innovation in the synthetic methodologies. Some natural sources and isolation techniques were described. Different pharmacological applications have also been claimed. Two of the most studied applications have been the use of these compounds as therapeutic agents for cancer and skin diseases. Some safety requirements need to be developed in order to find new chemical entities as new drugs.

Abstract A computational study has been performed for protonated oxygen- or nitrogen-containing heterocyclic derivatives of cyclopropane and cyclopropanone. We have searched for the most stable conformations of the protonated species using density functional theory with the B3LYP functional and the 6-31G(2df,p) basis set. More accurate enthalpy values were obtained from G4 calculations. Proton affinities and gas-phase basicities were accordingly derived.