Tris{2-[(2-amino­benzyl­idene)amino]­ethyl}amine

The title Schiff base, C27H33N7, is a tripodal amine displaying C 3 symmetry, with the central tertiary N atom lying on the threefold crystallographic axis. The N—CH2—CH2—N conformation of the pendant arms is gauche [torsion angle = 76.1 (3)°], which results in a claw-like mol­ecule, with the terminal aniline groups wrapped around the symmetry axis. The lone pair of the apical N atom is clearly oriented inwards towards the cavity, and should thus be chemically inactive. The amine NH2 substituents lie in the plane of the benzene ring to which they are bonded. With such an arrangement, one amine H atom forms an S(6) motif through a weak N—H⋯N hydrogen bond with the imine N atom, while the other is engaged in an inter­molecular N—H⋯π contact involving the benzene ring of a neighbouring mol­ecule related by inversion. The benzene rings also participate in an intra­molecular C—H⋯π contact of similar strength. In the crystal structure, mol­ecules are separated by empty voids (ca 5% of the crystal volume), although the crystal seems to be unsolvated

Retos actuales de la farmacia

Retos actuales de la farmacia es un proyecto que está coordinado por Leobargo Manuel Gómez Oliván y un equipo de investigadores que forman parte del claustro de la Facultad de Química en el área de posgrado, ellos han incentivado el espíritu investigador y científico de los estudiantes adscritos al programa para adentrarse en el ámbito farmacéutico. Los capítulos que conforman esta edición son el reflejo de la actividad académica desarrollada en este posgrado en las diferentes áreas de acentuación que lo conforman: farmacia molecular, farmacia social y tecnología farmacéutica

Self-Assembly behavior of amphiphilic janus dendrimers in water: a combined experimental and coarse-grained molecular dynamics simulation approach

Amphiphilic Janus dendrimers (JDs) are repetitively branched molecules with\ua0hydrophilic and hydrophobic components that self-assemble in water to form a variety of\ua0morphologies, including vesicles analogous to liposomes with potential pharmaceutical\ua0and medical application. To date, the self-assembly of JDs has not been fully\ua0investigated thus it is important to gain insight into its mechanism and dependence on\ua0JDs’ molecular structure. In this study, a series of amphiphilic JDs with variations in their\ua0core and branching pattern was synthesized and its aggregation behavior in water was\ua0evaluated using experimental and computational methods. JDs were obtained from 2,2-bis(hydroxymethyl)propionic acid, myristic acid and different glycols. Dispersions of JDs\ua0in water were carried out using the thin-film hydration, solvent injection methods and by\ua0microfluidics, using double emulsion drops with ultrathin shells as templates.\ua0Furthermore, a coarse-grained molecular dynamics (CG-MD) simulation was performed\ua0to study the mechanism of JDs aggregation. The resulting assemblies were\ua0characterized by optical microscopy, dynamic light scattering, confocal microscopy, and\ua0atomic force microscopy. The obtaining of assemblies in water with no interdigitated\ua0bilayers was confirmed by the experimental characterization and CG-MD simulation for\ua0one of the dendrimers. Assemblies with dendrimersome characteristics were obtained\ua0using the solvent injection method. Also,\ua0monodisperse nanometric assemblies were\ua0obtained by this method. The use of microfluidics enables the production of giant\ua0dendrimersomes from highly hydrophobic JDs, even when the dendrimers did not form\ua0vesicles using the thin-film hydration method. The results of this study establish a\ua0relationship between the molecular structure of the JDs and the properties of its\ua0aggregates in water. These results could be relevant for the design of novel JDs with\ua0tailored assemblies suitable for drug delivery systems. In addition, this study offers an\ua0approach to produce dendrimersomes in a more controlled way

Ex Vivo Cardiotoxicity of Antineoplastic Casiopeinas Is Mediated through Energetic Dysfunction and Triggered Mitochondrial-Dependent Apoptosis

Casiopeinas are a group of copper-based antineoplastic molecules designed as a less toxic and more therapeutic alternative to cisplatin or Doxorubicin; however, there is scarce evidence about their toxic effects on the whole heart and cardiomyocytes. Given this, rat hearts were perfused with Casiopeinas or Doxorubicin and the effects on mechanical performance, energetics, and mitochondrial function were measured. As well, the effects of Casiopeinas-triggered cell death were explored in isolated cardiomyocytes. Casiopeinas III-Ea, II-gly, and III-ia induced a progressive and sustained inhibition of heart contractile function that was dose- and time-dependent with an IC50 of 1.3 ± 0.2, 5.5 ± 0.5, and 10 ± 0.7 μM, correspondingly. Myocardial oxygen consumption was not modified at their respective IC50, although ATP levels were significantly reduced, indicating energy impairment. Isolated mitochondria from Casiopeinas-treated hearts showed a significant loss of membrane potential and reduction of mitochondrial Ca2+ retention capacity. Interestingly, Cyclosporine A inhibited Casiopeinas-induced mitochondrial Ca2+ release, which suggests the involvement of the mitochondrial permeability transition pore opening. In addition, Casiopeinas reduced the viability of cardiomyocytes and stimulated the activation of caspases 3, 7, and 9, demonstrating a cell death mitochondrial-dependent mechanism. Finally, the early perfusion of Cyclosporine A in isolated hearts decreased Casiopeinas-induced dysfunction with reduction of their toxic effect. Our results suggest that heart cardiotoxicity of Casiopeinas is similar to that of Doxorubicin, involving heart mitochondrial dysfunction, loss of membrane potential, changes in energetic metabolites, and apoptosis triggered by mitochondrial permeability