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1.
Alexey E. Machulkin Dmitry A. Skvortsov Yan A. Ivanenkov Anton P. Ber Mikhail V. Kavalchuk Anastasia V. Aladinskaya Anastasia A. Uspenskaya Radik R. Shafikov Ekaterina A. Plotnikova Raisa I. Yakubovskaya Ekaterina A. Nimenko Nikolay U. Zyk Elena K. Beloglazkina Nikolay V. Zyk Victor E Koteliansky Alexander G. Majouga 《Bioorganic & medicinal chemistry letters》2019,29(16):2229-2235
Prostate cancer (PC) is the second most commonly occurring cancer in men. Conventional chemotherapy has wide variety of disadvantages such as high systemic toxicity and low selectivity. Targeted drug delivery is a promising approach to decrease side effects of therapy. Prostate specific membrane antigen (PSMA) is overexpressed in prostate cancer cells while low level of expression is observed in normal cells. In this study we describe the development of Glu-urea-Lys based PSMA-targeting conjugates with paclitaxel. A series of new PSMA targeting conjugates with paclitaxel was designed and synthesized. The cytotoxicity of conjugates was evaluated against prostate (LNCaP, 22Rv1 and PC-3) and non-prostate (Hek293T, VA13, A549 and MCF-7) cell lines. The most promising conjugate 21 was examined in vivo using 22Rv1 xenograft mice model. It demonstrated good efficiency comparable with paclitaxel, while reduced toxicity. 3D molecular docking study was also performed to understand underlying mechanism of binding and further optimization of the linker substructure and conjugates structure for improving the target affinity. These conjugates may be useful for further design of novel PSMA targeting delivery systems for PC. 相似文献
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The paper presents a method for syndromic surveillance of an epidemic outbreak due to an emerging disease, formulated in the context of stochastic nonlinear filtering. The dynamics of the epidemic is modeled using a stochastic compartmental epidemiological model with inhomogeneous mixing. The syndromic (typically non-medical) observations of the number of infected people (e.g. visits to pharmacies, sale of certain products, absenteeism from work/study, etc.) are assumed available for monitoring and prediction of the epidemic. The state of the epidemic, including the number of infected people and the unknown parameters of the model, are estimated via a particle filter. The numerical results indicate that the proposed framework can provide useful early prediction of the epidemic peak if the uncertainty in prior knowledge of model parameters is not excessive. 相似文献
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L. D. Smirnov Yu. V. Kuznetsov S. Ya. Proskuryakov V. G. Skvortsov T. N. Nosko A. E. Dontsov 《Biophysics》2011,56(2):276-280
The antiradical and NO-inhibiting activities of β-hydroxy(ethoxy) derivatives of nitrous heterocycles (3-hydroxypyridine,
5-hydroxybenzimodazole, and 6-hydroxy(alkoxy)-benzothiazole) have been studied. The antiradical activity has been studied
using a homogeneous hydrophilic chemiluminescent system, and the quenching constants (K
i
) have been determined. For the most reactive compound, 4-methylthiobenzimidazolyl-3-hydroxypyridine, K
i
= 4.5 × 105 M−1. The NO-inhibiting activity was estimated on a model of the endotoxin shock of experimental animals using a spin trap of
nitric oxide radicals based on complexes of iron with sodium diethyldithiocarbamate. It was found that the compounds at doses
of 0.25–1 mmol/kg have both the inhibitory and stimulating action on the production of nitric oxide in the liver of animals.
The results obtained suggest that some derivatives of nitrous heterocycles can be used as effective antioxidant preparations. 相似文献
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Ludmila V. Puchkova Alexey N. Skvortsov Paolo Rusconi Ekaterina Yu. Ilyechova Massimo Broggini 《Biometals》2016,29(5):841-849
Cisplatin is a widely used antitumor agent; however, tumor resistance and severe side effects limit its use. It is well accepted that cisplatin toxicity can be modulated in vitro in cell cultures by copper salts. In the present work, mice with different blood serum copper status were treated with a single intraperitoneal cisplatin injection at a dose of 5 mg/kg, monitored for 3 days in metabolic cages and analyzed for renal function. Both copper-deficient and copper-overloaded mice displayed more severe early proteinuria and retarded platinum excretion than control mice. The effects of copper status on cisplatin-induced nephrotoxicity are discussed. 相似文献