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Myriam Gonzlez María Ovejero-Snchez Alba Vicente-Blzquez Raquel lvarez Ana B. Herrero Manuel Medarde Rogelio Gonzlez-Sarmiento Rafael Pelez 《International journal of molecular sciences》2021,22(4)
Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most commonly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes—first-line treatments—turn the development of alternative therapeutics into an urgency. Taxanes exhibit low water solubility that require formulations that involve side effects. These drugs are often associated with dose-limiting toxicities and with the appearance of multi-drug resistance (MDR). Here, we propose targeting tubulin with compounds directed to the colchicine site, as their smaller size offer pharmacokinetic advantages and make them less prone to MDR efflux. We have prepared 52 new Microtubule Destabilizing Sulfonamides (MDS) that mostly avoid MDR-mediated resistance and with improved aqueous solubility. The most potent compounds, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methylaminobenzenesulfonamide 38, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 42, and N-benzyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 45 show nanomolar antiproliferative potencies against ovarian, breast, and cervix carcinoma cells, similar or even better than paclitaxel. Compounds behave as tubulin-binding agents, causing an evident disruption of the microtubule network, in vitro Tubulin Polymerization Inhibition (TPI), and mitotic catastrophe followed by apoptosis. Our results suggest that these novel MDS may be promising alternatives to taxane-based chemotherapy in chemoresistant Pan-Gyn cancers. 相似文献
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Lorena Rodríguez-López Myriam Rincón-Fontán Xanel Vecino Ana B. Moldes Jose M. Cruz 《Journal of surfactants and detergents》2020,23(1):79-90
Over the last few years, the global biosurfactant market has raised due to the increasing awareness among consumers, for the use of biological or bio-based products. Because of their composition, it can be speculated that these are more biocompatible and more biodegradable than their chemical homologous. However, at the moment, no studies exist in the literature about the biodegradability of biosurfactants. In this work, a biosurfactant contained in a crude extract, obtained from a corn wet-milling industry stream that ferments spontaneously in the presence of lactic acid bacteria, was subjected to a biodegradation study, without addition of external microbial biomass, under different conditions of temperature (5–45 °C), biodegradation time (15–55 days), and pH (5–7). For that, a Box–Behnken factorial design was applied, which allowed to predict the percentage of biodegradation for the biosurfactant contained in the crude extract, between the range of the independent variables selected in the study, obtaining biodegradation values between 3 and 80%. The percentage of biodegradation for the biosurfactant was calculated based on the increase in the surface tension of samples of the crude extract. Furthermore, it was also possible to predict the variation in t1/2 for the biosurfactant (time to achieve the 50% of biodegradation) under different conditions. 相似文献
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Jean-Louis Havet Myriam Billiau-Loreau Catherine Porte Alain Delacroix 《Journal of Automated Methods and Management in Chemistry》2002,24(4):111-119
Chemometric tools were used to generate the modelling of solvent e inverted exclamation markects on the N-alkylation of an isocyanuric acid salt. The method proceeded from a central composite design applied on the Carlson solvent classification using principal components analysis. The selectivity of the reaction was studied from the production of different substituted isocyanuric derivatives. Response graphs were obtained for each compound and used to devise a strategy for solvent selection. The prediction models were validated and used to search for the best selectivity for the reaction system. The solvent most often selected as the best for the reaction is the N,N-dimethylformamide. 相似文献
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D. Trmouilles G. Bertrand M. Bafleur F. Beaudoin P. Perdu N. Guitard L. Lescouzres 《Microelectronics Reliability》2003,43(1):71-79
The number of circuit design iterations due to electrostatic discharge (ESD) failures increases with the complexity of VLSI technologies and their shrinking. In this paper, we show how TCAD and ESD SPICE modeling can be used to solve ESD protection issues in an analog CMOS technology. 相似文献
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Reports an error in "Current issues relating to psychosocial job strain and cardiovascular disease research" by T?res Theorell and Robert A. Karasek (Journal of Occupational Health Psychology, 1996[Jan], Vol 1[1], 9-26). On p. 12, in the caption to Figure 2, the copyright statement is missing. The caption should have read "The environment, the worker, and illness: Dynamic associations linking environmental strain and learning to evolution of personality. From Healthy Work: Stress, Productivity, and the Reconstruction of Working Life (p. 99), by R. A. Karasek and T. Theorell, 1990, New York: Basic Books. Copyright 1990 by Basic Books. Used with permission." (The following abstract of the original article appeared in record 1996-04477-002.) Examines recent reviews of cardiovascular (CV) job strain (JS) research by P. L. Schnall and P. A. Landsbergis (1994) and T. S. Kristensen (see record 1995-39109-001), which conclude that JS as defined by the demand-control model (the combination of contributions of low job decision latitudes and high psychological job demands) is confirmed as a risk factor for CV mortality in a large majority of studies. Lack of social support at work appears to increase this risk. Several still-unresolved issues are discussed in light of recent research. Methodological issues related to the use of occupational & career aggregate estimates, use of standard scales for job analysis, and recall bias in issues of self-reporting are examined. Confounding factors and differential strengths of associations by subgroups in JS-CV disease analyses with respect to social class, gender, and working hours are addressed. A review of results of monitoring JS-blood pressure associations and associated methodological issues is provided. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献