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71.
Julio Caballero Szymon Zilocchi William Tiznado Daniela Rossi Simona Collina 《Molecular simulation》2013,39(3):227-235
Sigma-1 (σ1) affinities of methyl 2-(aminomethyl)-1-phenylcyclopropane-1-carboxylate (MAPCC) derivatives were modelled by the genetic algorithm with linear assignment of hypermolecular alignment of datasets (GALAHAD) and the comparative molecular field analysis (CoMFA)/comparative molecular similarity indices analysis (CoMSIA) methods. GALAHAD was used for deriving the 3D pharmacophore pattern that encompasses the most potent σ1 ligands within this series. Five MAPCC derivatives with a high σ1 affinity were used for deriving this model. The obtained model included a nitrogen atom, the hydrophobes and the hydrogen bond acceptor features; it was able to identify other potent σ1 ligands. On the other hand, CoMFA and CoMSIA methods were used for deriving quantitative structure–activity relationship (QSAR) models. All QSAR models were trained with 17 compounds, after which they were evaluated for predictive ability with additional five compounds. The best QSAR model was obtained by using CoMSIA, including steric, electrostatic and hydrophobic fields, and had a good predictive quality according to both internal and external validation criteria. In general, the models described herein provide meaningful information relevant for the rational design of new σ1 ligands. 相似文献
72.
73.
María Lorena Falcone Ferreyra Eduardo Rodriguez María Isabel Casas Guillermo Labadie Erich Grotewold Paula Casati 《The Journal of biological chemistry》2013,288(44):31678-31688
Flavonoids accumulate in plant vacuoles usually as O-glycosylated derivatives, but several species can also synthesize flavonoid C-glycosides. Recently, we demonstrated that a flavanone 2-hydroxylase (ZmF2H1, CYP93G5) converts flavanones to the corresponding 2-hydroxy derivatives, which are expected to serve as substrates for C-glycosylation. Here, we isolated a cDNA encoding a UDP-dependent glycosyltransferase (UGT708A6), and its activity was characterized by in vitro and in vivo bioconversion assays. In vitro assays using 2-hydroxyflavanones as substrates and in vivo activity assays in yeast co-expressing ZmF2H1 and UGT708A6 show the formation of the flavones C-glycosides. UGT708A6 can also O-glycosylate flavanones in bioconversion assays in Escherichia coli as well as by in vitro assays with the purified recombinant protein. Thus, UGT708A6 is a bifunctional glycosyltransferase that can produce both C- and O-glycosidated flavonoids, a property not previously described for any other glycosyltransferase. 相似文献
74.
Marco Fidani Maria C. Gamberini Giuseppe Pompa Francesca Mungiguerra Alessio Casati Francesco Arioli 《Steroids》2013,78(2):121-126
The possibility of an endogenous presence of the glucocorticoid prednisolone has already been demonstrated in bovine and horse urine, with the aim of clarifying its origin in this matrix, which is used by official agencies for the control of illicit treatments. From this point of view, the endogenous nature of prednisolone could be a major topic in doping control of both amateur and professional human athletes. A study was therefore made on 34 human volunteers (13 males and 21 females; aged 22–62) to detect the presence of prednisolone in their urine by HPLC–MS3. One of the volunteers underwent vernal allergy treatment with betamethasone for two subsequent years. An investigation was carried out with the aim of verifying if the suppression, and the circadian rhythm, of cortisol urinary levels could also apply to prednisolone. The results of the study show that prednisolone was present in the urine of all 34 volunteers, with a concentration very close to 100-times lower that of cortisol, with no dependence on gender. The same ratio (1/100) was observed in the prednisolone and cortisol levels detected during the 24 h together with the suppression of prednisolone by betamethasone treatment.These data demonstrate the endogenous nature of low concentrations of prednisolone in human urine, and motivate further studies about the biosynthetic pathways of this corticosteroid and its relationship with stress in humans, as already described in cows. 相似文献
75.
Capsule?Of 26 species of wintering waterbirds, 18 showed an increase in numbers, five showed a decrease and two showed no change. Aim?To assess long-term trends in the numbers and distribution of the 26 most abundant wintering waterbird species in the Czech Republic. Methods?We used International Waterbird Census data from between 48 and 639 wetland sites which had been counted annually in the Czech Republic from 1966 to 2008. From these data long-term changes in numbers and distributions were determined. Log-linear Poisson regression analysis was used to estimate missing data using trim software. The distribution of each species was described as the ratio of the number of sites occupied by that species to the total number of sites investigated. Results?Increasing trends were found for 18 species, five species were found to be declining, one species was stable and two species were found with uncertain trends. Wintering distributions (the ratio of sites occupied by a given species to the total number of sites counted) increased in 16 species and decreased in two species, broadly correlated with the species changes in numbers. Conclusion?In most species changes in numbers as well as changes in distribution followed the Western Palearctic population trends. Those species which increased were mainly piscivores and included geese, ducks and gulls. Scarcer species also exhibited an increase in numbers. The changes in numbers (both positive and negative) were more frequent among species associated with running water, whereas species which showed uncertain trends were more frequently recorded on standing water, which is more affected by variable weather conditions. 相似文献
76.
The objective of the current study is to develop a new cryomacroscope prototype for the study of vitrification in large-size specimens. The unique contribution in the current study is in developing a cryomacroscope setup as an add-on device to a commercial controlled-rate cooler and in demonstration of physical events in cryoprotective cocktails containing synthetic ice modulators (SIM)—compounds which hinder ice crystal growth. Cryopreservation by vitrification is a highly complex application, where the likelihood of crystallization, fracture formation, degradation of the biomaterial quality, and other physical events are dependent not only upon the instantaneous cryogenic conditions, but more significantly upon the evolution of conditions along the cryogenic protocol. Nevertheless, cryopreservation success is most frequently assessed by evaluating the cryopreserved product at its end states—either at the cryogenic storage temperature or room temperature. The cryomacroscope is the only available device for visualization of large-size specimens along the thermal protocol, in an effort to correlate the quality of the cryopreserved product with physical events. Compared with earlier cryomacroscope prototypes, the new Cryomacroscope-III evaluated here benefits from a higher resolution color camera, improved illumination, digital recording capabilities, and high repeatability in tested thermal conditions via a commercial controlled-rate cooler. A specialized software package was developed in the current study, having two modes of operation: (a) experimentation mode to control the operation of the camera, record camera frames sequentially, log thermal data from sensors, and save case-specific information; and (b) post-processing mode to generate a compact file integrating images, elapsed time, and thermal data for each experiment. The benefits of the Cryomacroscope-III are demonstrated using various tested mixtures of SIMs with the cryoprotective cocktail DP6, which were found effective in preventing ice growth, even at significantly subcritical cooling rates with reference to the pure DP6. 相似文献
77.
Simona Maria Monti Giuseppina De Simone Nina A. Dathan Martha Ludwig Daniela Vullo Andrea Scozzafava Clemente Capasso Claudiu T. Supuran 《Bioorganic & medicinal chemistry letters》2013,23(6):1626-1630
Several β-carbonic anhydrases (CAs, EC 4.2.1.1) are present in all land plants examined thus far. Here we report the first detailed biochemical characterization of one such isoform, FbiCA 1, from the C4 plant Flaveria bidentis, which was cloned, purified and characterized as recombinant protein. FbiCA 1 has an interesting CO2 hydrase catalytic activity (kcat of 1.2 × 105 and kcat/Km of 7.5 × 106 M?1 × s?1) and was moderately inhibited by most simple/complex inorganic anions. Potent FbiCA 1 inhibitors were also detected, such as trithiocarbonate, diethyldithiocarbamate, sulfamide, sulfamic acid, phenylboronic acid and phenylarsonic acid (KIs in the range of 4–60 μM). Such inhibitors may be used as tools to better understand the role of various β-CA isoforms in photosynthesis. 相似文献
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79.
Lisa Dalla Via Aída N. García-Argáez Arianna Adami Silvia Grancara Pamela Martinis Antonio Toninello Daniela Belli Dell’Amico Luca Labella Simona Samaritani 《Bioorganic & medicinal chemistry》2013,21(22):6965-6972
A convenient synthetic route and the characterization of complexes trans-[PtCl2(L)(PPh3)] (L = Et2NH (2), (PhCH2)2NH (3), (HOCH2CH2)2NH) (4) are reported. The antiproliferative activity was evaluated on three human tumor cell lines. The investigation on the mechanism of action highlighted for the most active complex 4 the capacity to affect mitochondrial functions. In particular, both the induction of the mitochondrial permeability transition phenomenon and an aspecific membrane damage occurred, depending on concentration. 相似文献
80.
Claudio Battilocchio Giovanna Poce Salvatore Alfonso Giulio Cesare Porretta Sara Consalvi Lidia Sautebin Simona Pace Antonietta Rossi Carla Ghelardini Lorenzo Di Cesare Mannelli Silvia Schenone Antonio Giordani Luigia Di Francesco Paola Patrignani Mariangela Biava 《Bioorganic & medicinal chemistry》2013,21(13):3695-3701
We report the synthesis and bio-pharmacological evaluation of a class of pyrrole derivatives featuring a small appendage fragment (carbaldehyde, oxime, nitrile) on the central core. Compound 1c proved to be extremely effective in vivo, showing an interesting anti-nociceptic profile that is comparable to reference compounds already marketed, hence representing a great stimulus for a further improvement of this class of molecules. 相似文献