Síntesis, caracterización y estudios de hidrólisis de complejos trans-[PtCl2(15N-amina)(15N-amina')] por RMN 2D [1H,15N] HSQC: citotoxicidad y fotoquímica de complejos de PtII y PtIV

Tesis doctoral inédita. Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Inorgánica. Fecha de lectura: 19-12-200

Synthesis, reactivity studies, and cytotoxicity of two trans-Iodidoplatinum(II) complexes. Does photoactivation work?

trans-Platinum complexes have been the landmark in unconventional drugs prompting the development of innovative structures that might exhibit chemical and biological profiles different to cisplatin. Iodido complexes signaled a new turning point in the platinum drug design field when their cytotoxicity was reevaluated and reported. In this new study, we have synthesized and evaluated diodidoplatinum complexes trans-[PtI2(amine)(pyridine)] bearing aliphatic amines (isopropylamine and methylamine) and pyridines in trans configuration. X-ray diffraction data support the structural characterization. Their cytotoxicity has been evaluated in tumor cell lines such as SAOS-2, A375, T-47D, and HCT116. Moreover, we report their solution behavior and reactivity with biological models. Ultraviolet-a (UVA) irradiation induces an increase in their reactivity towards model nucleobase 5′-GMP in early stages, and promotes the release of the pyridine ligand (spectator ligand) at longer reaction times. Density Functional calculations have been performed and the results are compared with our previous studies with other iodido derivatives.MINECO CTQ-2015-68779

Photoactivation of trans diamine platinum complexes in aqueous solution and effect on reactivity towards nucleotides

We show that UVA irradiation (365 nm) of the Pt-IV complex trans,trans,trans-[(PtCl2)-Cl-IV(OH)(2)(dimethylamine) (isopropylamine)] (1), induces reduction to Pt-II photoproducts. For the mixed amine Pt-II complex, trans[(PtCl2)-Cl-II(isopropylamine)(methylamine)] (2), irradiation at 365 nm increases the rate and extent of hydrolysis, triggering the formation of diaqua species. Additionally, irradiation increases the extent of reaction of complex 2 with guanosine-5'-monophosphate and affords mainly the bis-adduct, while reactions with adenosine-5'-monophosphate and cytidine-5'-monophosphate give rise only to mono-nucleotide adducts. Density Functional Theory calculations have been used to obtain insights into the electronic structure of complexes 1 and 2, and their photophysical and photochemical properties. UVA-irradiation can contribute to enhanced cytotoxic effects of diamine platinum drugs with trans geometry

Trans platinum complexes design: One novel water soluble oxime derivative that contains aliphatic amines in trans configuration

7 páginas, 5 figuras, 1 tabla -- PAGS nros. 104-110In an attempt to design new antitumoral drugs based on transplatin complexes, we determined the experimental conditions for the preparation of trans-[Pt((CH3)2CNOH)((CH3)2CHNH2)Cl2], and solved the crystal structure. The cytotoxicity of the novel complex, the cis counterpart, cisplatin, and a trans complex with aliphatic amines, as well as the capacity of some of these complexes to cause either apoptotic or necrotic cell death, was comparatively examined in NRK-52E rat renal tubular cells and HepG2 human hepatoma cells. The results indicate that the oxime complex with trans geometry, but not the one with cis geometry, causes death by apoptosis, making the complex potentially suitable for therapeutic purposes. However cytotoxicity values are higher in the case of cis geometry than in trans geometry in both tumoral and non-tumoral cell linesAuthors thank the Spanish Ministry of Science and Education, Spanish CICYT Grants: SAF2003-01700 and SAF2004-01250Peer reviewe

Assembly of Palladium(II) and Platinum(II) Metallo-Rectangles with a Guanosine-Substituted Terpyridine and Study of Their Interactions with Quadruplex DNA

International audienceTwo novel [2+2] metallo-assemblies based on a guanosine-substituted terpyridine ligand (1) coordinated to palladium(II) (2a) and platinum(II) (2b) are reported. These supramolecular assemblies have been fully characterized by NMR spectroscopy, ESI mass spectrometry and elemental analyses. The palladium(II) complex (2a) has also been characterized by single crystal X-ray diffraction studies confirming that the system is a [2+2] metallo-rectangle in the solid state. The stabilities of these [2+2] assemblies in solution have been confirmed by DOSY studies as well as by variable temperature 1H NMR spectroscopy. The ability of these di-nuclear complexes to interact with quadruplex and duplex DNA was investigated by Fluorescent Intercalator Displacement (FID) assays, Fluorescence Resonance Energy Transfer (FRET) meting studies, and electrospray mass spectrometry (ESI-MS). These studies have shown that both these assemblies interact selectively with quadruplex DNA (human telomeric DNA and the G-rich promoter region of c-Myc oncogene) over duplex DNA, and are able to induce dimerization of parallel G-quadruplex structures

Locomotion and gait disorders

El ser humano se caracteriza por la especialización de determinadas funciones, como son el lenguaje o la marcha. Esta capacidad la hemos llevado a cabo gracias al desarrollo de múltiples interconexiones entre diferentes áreas del sistema nervioso central y periférico, así como a la adaptación musculoesquelética. Todas ellas son fundamentales para una correcta realización de la deambulación y el mantenimiento del equilibrio. Los trastornos de la marcha, en la actualidad, están cobrando especial importancia en las consultas de neurología, hecho que está directamente relacionado con el fenómeno de envejecimiento de la población, dado que es una patología especialmente prevalente en la población anciana. Uno de los pilares básicos en el estudio de estos trastornos es la diferenciación de los distintos patrones clínicos de marcha y la clasificación según el sistema neuronal dañado. La observación, el empleo de diferentes maniobras en la exploración y la búsqueda de otros signos clínicos asociados nos permiten una buena aproximación diagnóstica, que posteriormente podremos confirmar con técnicas complementarias más específicas.Human beings are characterised by the specialisation of certain functions, such as language or the ability to walk. We have achieved this capacity thanks to the development of multiple connections among different areas of the central and peripheral nervous system, together with adaptation of the musculoskeletal system. These are all essential to be able to walk correctly and to keep our balance. Gait disorders are currently receiving a great deal of attention in neurology departments, and this fact is directly related to the phenomenon of the ageing of the population, since it is a pathology that is particularly prevalent among the elderly. One of the fundamental mainstays in the study of these disorders is being able to distinguish between the different clinical gait patterns and their classification according to the neural system that has been damaged. Observation, the use of different manoeuvres in the examination and the search for other associated clinical signs all enable us reach a good diagnostic approximation, which will later be confirmed with more specific complementary techniques

Digestive disorders in Parkinson's disease: dysphagia and sialorrhea

Los síntomas no motores de la enfermedad de Parkinson representan un trastorno frecuente y a menudo infradiagnosticado. Entre los diferentes síntomas no motores cabe destacar la disfagia y la sialorrea, relativamente habituales en estadios avanzados de la enfermedad por su importante repercusión funcional y por la comorbilidad asociada.The non-motor symptoms of Parkinson’s disease are a frequent and often under-diagnosed disorder. Two of the most significant non-motor symptoms are perhaps dysphagia and sialorrhea (which are relatively common in advanced stages of the disease) owing to their important functional repercussions and to the associated comorbidity

SWEDDs: scans without evidence of dopaminergic deficit

Aproximadamente un 10% de los pacientes diagnosticados inicialmente de Enfermedad de Parkinson (E.P.), no presentan alteraciones en la vía dopaminérgica nigroestriatal en su vertiente presináptica; se engloban bajo el acrónimo SWEDDs (Scans without evidence of dopaminergic deficit).Approximately 10% of all patients initially diagnosed with Parkinson's disease (PD) do not present any alterations in the presynaptic nigrostriatal dopaminergic pathway; they are classified under the acronym SWEDDs (Scans without evidence of dopaminergic deficit)

Back Cover: Quadruplex DNAâ Stabilising Dinuclear Platinum(II) Terpyridine Complexes with Flexible Linkers (Chem. Eur. J. 7/2016)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137289/1/chem201600136.pd