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Mariana Pazos Estefania Dibello Juan Manuel Mesa Dalibor Sames Marcelo Alberto Comini Gustavo Seoane Ignacio Carrera 《Molecules (Basel, Switzerland)》2022,27(3)
The first stage of the drug discovery process involves the identification of small compounds with biological activity. Iboga alkaloids are monoterpene indole alkaloids (MIAs) containing a fused isoquinuclidine-tetrahydroazepine ring. Both the natural products and the iboga-inspired synthetic analogs have shown a wide variety of biological activities. Herein, we describe the chemoenzymatic preparation of a small library of novel N-indolylethyl-substituted isoquinuclidines as iboga-inspired compounds, using toluene as a starting material and an imine Diels–Alder reaction as the key step in the synthesis. The new iboga series was investigated for its potential to promote the release of glial cell line-derived neurotrophic factor (GDNF) by C6 glioma cells, and to inhibit the growth of infective trypanosomes. GDNF is a neurotrophic factor widely recognized by its crucial role in development, survival, maintenance, and protection of dopaminergic neuronal circuitries affected in several neurological and psychiatric pathologies. Four compounds of the series showed promising activity as GDNF releasers, and a leading structure (compound 11) was identified for further studies. The same four compounds impaired the growth of bloodstream Trypanosoma brucei brucei (EC50 1–8 μM) and two of them (compounds 6 and 14) showed a good selectivity index. 相似文献
13.
lvaro Fernndez-Ochoa María de la Luz Cdiz-Gurrea Patricia Fernndez-Moreno Alejandro Rojas-García David Arrez-Romn Antonio Segura-Carretero 《Molecules (Basel, Switzerland)》2022,27(3)
The study of the bioavailability of bioactive compounds is a fundamental step for the development of applications based on them, such as nutraceuticals, functional foods or cosmeceuticals. It is well-known that these compounds can undergo metabolic reactions before reaching therapeutic targets, which may also affect their bioactivity and possible applications. All recent studies that have focused on bioavailability and metabolism of phenolic and terpenoid compounds have been developed because of the advances in analytical chemistry and metabolomics approaches. The purpose of this review is to show the role of analytical chemistry and metabolomics in this field of knowledge. In this context, the different steps of the analytical chemistry workflow (design study, sample treatment, analytical techniques and data processing) applied in bioavailability and metabolism in vivo studies are detailed, as well as the most relevant results obtained from them. 相似文献
14.
Norbert Schuch J. Ignacio Cirac Michael M. Wolf 《Communications in Mathematical Physics》2006,267(1):65-92
We investigate bosonic Gaussian quantum states on an infinite cubic lattice in arbitrary spatial dimensions. We derive general properties of such states as ground states of quadratic Hamiltonians for both critical and non-critical cases. Tight analytic relations between the decay of the interaction and the correlation functions are proven and the dependence of the correlation length on band gap and effective mass is derived. We show that properties of critical ground states depend on the gap of the point-symmetrized rather than on that of the original Hamiltonian. For critical systems with polynomially decaying interactions logarithmic deviations from polynomially decaying correlation functions are found. 相似文献
15.
Ignacio Moreno Pablo Velásquez Daniel Puerto Asticio Vargas 《Optics Communications》2006,260(1):12-18
In this work, we show a very simple birefringent filter useful to modulate a broadband light spectrum. We first show the generation of various oscillating spectra using two identical multiple-order waveplates. In particular a sinusoidal broadband spectrum with a rapid oscillation is obtained. This spectrum is amplitude modulated by adding another waveplate to the system. This waveplate has a small phase shift, and with the proper orientation generates amplitude beats on the broadband spectrum. Finally, we show how this system can be voltage controlled by means of a ferroelectric liquid crystal modulator. We experimentally demonstrate this behavior with the aid of a portable spectrophotometer, and we provide a theoretical explanation on the basis of the Jones matrix formalism. 相似文献
16.
Krauter H Muschik CA Jensen K Wasilewski W Petersen JM Cirac JI Polzik ES 《Physical review letters》2011,107(8):080503
Entanglement is a striking feature of quantum mechanics and an essential ingredient in most applications in quantum information. Typically, coupling of a system to an environment inhibits entanglement, particularly in macroscopic systems. Here we report on an experiment where dissipation continuously generates entanglement between two macroscopic objects. This is achieved by engineering the dissipation using laser and magnetic fields, and leads to robust event-ready entanglement maintained for 0.04 s at room temperature. Our system consists of two ensembles containing about 10(12) atoms and separated by 0.5 m coupled to the environment composed of the vacuum modes of the electromagnetic field. By combining the dissipative mechanism with a continuous measurement, steady state entanglement is continuously generated and observed for up to 1 h. 相似文献
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Fernando Saldaña Ignacio Barradas 《Mathematical Methods in the Applied Sciences》2020,43(3):1216-1229
Persistent infection with human papillomavirus (HPV) is the main cause of cervical cancer. Current HPV vaccines protect against both HPV-16 and -18, which are known to cause approximately 70% of cervical cancer cases worldwide. These vaccines have shown to be highly effective in preventing infection by their targeted types. However, there is a broad diversity of HPV types not targeted by the vaccines, and there is controversy about a possible increase in the prevalence of these non-targeted types after a vaccination program. Here, we propose a within-host metapopulation model to study the possibility of vaccine-induced type replacement for oncogenic types. It is generally believed that the theoretical possibility of type replacement strongly depends on the existence of natural type competition mechanisms. Nevertheless, our results suggest that type replacement is viable at the within-host level if the degree of cross-protection induced by the vaccine is low, even if there is no underlying competition among HPV types. Consequently, the impact of current HPV vaccines at both the immunological and epidemiological levels rely upon the level of cross-protection. 相似文献
20.
Dr. Ignacio Colomer Dr. Mercedes Ureña Dr. Alma Viso Prof. Roberto Fernández de la Pradilla 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(20):4620-4632
The chemo- and stereocontrolled functionalization of conjugated sulfinyl dienes in a cascade process that involves a conjugate addition, diastereoselective protonation and a [2,3]-sigmatropic rearrangement is reported. Enantioenriched 1,4-diol and 1,4-aminoalcohol derivatives are obtained in a very straightforward manner. Further functionalization of these structures, including highly stereoselective epoxidation, dihydroxylation and the stereodivergent synthesis of several polyols in a controlled fashion is described. 相似文献