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11.
Andrey V. Markov Kirill V. Odarenko Aleksandra V. Senkova Oksana V. Salomatina Nariman F. Salakhutdinov Marina A. Zenkova 《Molecules (Basel, Switzerland)》2020,25(24)
Introduction of α-cyano α,β-unsaturated carbonyl moiety into natural cyclic compounds markedly improves their bioactivities, including inhibitory potential against tumor growth and metastasis. Previously, we showed that cyano enone-bearing derivatives of 18βH-glycyrrhetinic (GA) and deoxycholic acids displayed marked cytotoxicity in different tumor cell lines. Moreover, GA derivative soloxolone methyl (SM) was found to induce ER stress and apoptosis in tumor cells in vitro and inhibit growth of carcinoma Krebs-2 in vivo. In this work, we studied the effects of these compounds used in non-toxic dosage on the processes associated with metastatic potential of tumor cells. Performed screening revealed SM as a hit compound, which inhibits motility of murine melanoma B16 and human lung adenocarcinoma A549 cells and significantly suppresses colony formation of A549 cells. Further study showed that SM effectively blocked transforming growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) of A549 cells: namely, inhibited TGF-β-stimulated motility and invasion of tumor cells as well as loss of their epithelial characteristics, such as, an acquisition of spindle-like phenotype, up- and down-regulation of mesenchymal (vimentin, fibronectin) and epithelial (E-cadherin, zona occludens-1 (ZO-1)) markers, respectively. Network pharmacology analysis with subsequent verification by molecular modeling revealed that matrix metalloproteinases MMP-2/-9 and c-Jun N-terminal protein kinase 1 (JNK1) can be considered as hypothetical primary targets of SM, mediating its marked anti-EMT activity. The inhibitory effect of SM on EMT revealed in vitro was further confirmed in a metastatic model of murine B16 melanoma: SM was found to effectively block metastatic dissemination of melanoma B16 cells in vivo, increase expression of E-cadherin and suppress expression of MMP-9 in lung metastatic foci. Altogether, our data provided valuable information for a better understanding of the antitumor activity of cyano enone-bearing semisynthetic compounds and revealed SM as a promising anti-metastatic drug candidate. 相似文献
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O. V. Salomatina D. V. Korchagina Yu. V. Gatilov M. P. Polovinka V. A. Barkhash 《Russian Journal of Organic Chemistry》2004,40(10):1441-1449
Transformations of diepoxy derivatives of caryophyllene, a widely spread natural sesquiterpene, were studied in various acidic media under conditions of both homogeneous and heterogeneous catalysis. A number of previously unknown compounds were isolated. The experimental data were compared with the results of computer simulation of the most probable transformation pathways using molecular-mechanics and quantum-chemical methods.Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 10, 2004, pp. 1492–1499.Original Russian Text Copyright © 2004 by Salomatina, Korchagina, Gatilov, Polovinka, Barkhash. 相似文献
14.
Yarovaya O. I. Salomatina O. V. Korchagina D. V. Polovinka M. P. Barkhash V. A. 《Russian Journal of Organic Chemistry》2002,38(11):1594-1605
The transformations of 6,7-epoxy derivatives of widely spread in the nature unsaturated aldehydes, citral and citronellal, in various acidic media both under conditions of homogeneous and heterogeneous catalysis were investigated. A number of previously unknown products belonging to different classes of organic compounds was obtained. Probable mechanisms of the products formation are discussed. 相似文献
15.
Oksana V. Salomatina Nadezhda S. Dyrkheeva Irina I. Popadyuk Alexandra L. Zakharenko Ekaterina S. Ilina Nina I. Komarova Jhannes Reynisson Nariman F. Salakhutdinov Olga I. Lavrik Konstantin P. Volcho 《Molecules (Basel, Switzerland)》2022,27(1)
A series of deoxycholic acid (DCA) amides containing benzyl ether groups on the steroid core were tested against the tyrosyl-DNA phosphodiesterase 1 (TDP1) and 2 (TDP2) enzymes. In addition, 1,2,4- and 1,3,4-oxadiazole derivatives were synthesized to study the linker influence between a para-bromophenyl moiety and the steroid scaffold. The DCA derivatives demonstrated promising inhibitory activity against TDP1 with IC50 in the submicromolar range. Furthermore, the amides and the 1,3,4-oxadiazole derivatives inhibited the TDP2 enzyme but at substantially higher concentration. Tryptamide 5 and para-bromoanilide 8 derivatives containing benzyloxy substituent at the C-3 position and non-substituted hydroxy group at C-12 on the DCA scaffold inhibited both TDP1 and TDP2 as well as enhanced the cytotoxicity of topotecan in non-toxic concentration in vitro. According to molecular modeling, ligand 5 is anchored into the catalytic pocket of TDP1 by one hydrogen bond to the backbone of Gly458 as well as by π–π stacking between the indolyl rings of the ligand and Tyr590, resulting in excellent activity. It can therefore be concluded that these derivatives contribute to the development of specific TDP1 and TDP2 inhibitors for adjuvant therapy against cancer in combination with topoisomerase poisons. 相似文献
16.
O. V. Salomatina O. I. Yarovaya D. V. Korchagina Yu. V. Gatilov V. A. Barkhash 《Russian Journal of Organic Chemistry》2011,47(10):1479-1486
Transformations of diepoxy derivatives of terpinolene under conditions of homogeneous and heterogeneous acid catalysis were
studied. Qualitative and quantitative compositions of the reaction mixtures were found to depend on the acidity of the medium
and mutual orientation of the epoxide rings in the p-menthane skeleton. The experimental data were compared with the results of computer simulation of the most probable transformation
pathways in terms of molecular mechanics and quantum-chemical methods. 相似文献
17.
T. A. Gracheva T. A. Kuz’micheva V. N. Perevezentsev A. E. Mochalova L. A. Smirnova E. V. Salomatina 《Journal of Surface Investigation: X-ray, Synchrotron and Neutron Techniques》2011,5(3):426-430
The kinetics of UV-induced formation of gold nanoparticles in polymethylmethacrylate films doped with chloroauric acid HAuCl4 is studied. The films are investigated by the absorption spectroscopy and smallangle X-ray scattering methods. The changing size and polydispersity of gold nanoparticles are analyzed during their formation. The growth of gold nanoparticles is determined by the properties of a polymeric matrix and the rate of diffusion fluxes of matter. 相似文献