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31.
Aldar A. Munkuev Nadezhda S. Dyrkheeva Tatyana E. Kornienko Ekaterina S. Ilina Dmitry I. Ivankin Evgeniy V. Suslov Dina V. Korchagina Yuriy V. Gatilov Alexandra L. Zakharenko Anastasia A. Malakhova Jhannes Reynisson Konstantin P. Volcho Nariman F. Salakhutdinov Olga I. Lavrik 《Molecules (Basel, Switzerland)》2022,27(11)
Inhibiting tyrosyl-DNA phosphodiesterase 1 (TDP1) is a promising strategy for increasing the effectiveness of existing antitumor therapy since it can remove the DNA lesions caused by anticancer drugs, which form covalent complexes with topoisomerase 1 (TOP1). Here, new adamantane–monoterpene conjugates with a 1,2,4-triazole or 1,3,4-thiadiazole linker core were synthesized, where (+)-and (−)-campholenic and (+)-camphor derivatives were used as monoterpene fragments. The campholenic derivatives 14a–14b and 15a–b showed activity against TDP1 at a low micromolar range with IC50 ~5–6 μM, whereas camphor-containing compounds 16 and 17 were ineffective. Surprisingly, all the compounds synthesized demonstrated a clear synergy with topotecan, a TOP1 poison, regardless of their ability to inhibit TDP1. These findings imply that different pathways of enhancing topotecan toxicity other than the inhibition of TDP1 can be realized. 相似文献
32.
Irina V. Il'ina Konstantin P. Volcho Oksana S. Mikhalchenko Dina V. Korchagina Nariman F. Salakhutdinov 《Helvetica chimica acta》2011,94(3):502-513
The reactions of (?)‐cis‐verbenol epoxide with a number of aromatic aldehydes containing OH and/or MeO groups in the presence of montmorillonite K10 clay have been studied. Several new O‐containing heterocyclic compounds with different frameworks, including compounds with a previously unknown octahydro‐2H‐4,6‐(epoxymethano)chromene framework, have been synthesized. Introduction of one donor substituent in the benzaldehyde molecule led to a decrease in the total yield of intermolecular by formed products, while the introduction of two and more substituents led to an increase in the yield of these products. 相似文献
33.
Faramarz Rostami Charati Masoumeh Moghimi Malek Taher Maghsoodlou Sayyed M. Habibi-Khorassani Zinatossadat Hossaini Nariman Maleki 《Phosphorus, sulfur, and silicon and the related elements》2013,188(7):1428-1435
Abstract Protonation of the highly reactive 1:1 intermediate produced in the reaction between triphenylphosphite and activated acetylene by sulfonamide leads to a phosphonate ylide, which undergoes methanol elimination in the presence of moisture to produce a highly functionalized sulfonamide phosphonate diester. A dynamic nuclear magnetic resonance (NMR) effect is observed in the 1H NMR spectra of this compound as a result of restricted rotation around the single C?N bond. The coalescence temperature was observed at TC = 352.5 K, and the free energy of activation (ΔG#) for this process is 75.6 ± 2 kJ.mol?1. GRAPHICAL ABSTRACT 相似文献
34.
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
35.
Andrey V. Shernyukov Ilya Ya. Mainagashev Dina V. Korchagina Alexander M. Genaev Nina I. Komarova Nariman F. Salakhutdinov Genrikh A. Tolstikov 《Helvetica chimica acta》2013,96(9):1757-1781
The object of this study is the interaction of the cyclic anhydride 2 of (18α,19β)‐19‐hydroxy‐2,3‐secooleanane‐2,3,28‐trioic acid 28,19‐lactone ( 1 ) with primary and secondary amines. It was shown that the products of steric control (the corresponding 2‐amino‐2‐oxo‐3‐oic acids=2‐amides) were formed solely upon the opening of the anhydride cycle by secondary amines (Scheme 2), whereas the interaction with primary amines yielded a mixture of isomeric amides (Scheme 10). In the latter case, the solvent provided a noticeable effect on the reaction selectivity, which was demonstrated in the case of 4‐methoxybenzylamine. The interaction between the resulting 3‐amides and oxalyl chloride yielded the corresponding cyclic imides, whereas under these conditions, 2‐amides formed spiropyrrolidinetriones (Scheme 4). 相似文献
36.
Oksana S. Mikhalchenko Dina V. Korchagina Konstantin P. Volcho Nariman F. Salakhutdinov 《Helvetica chimica acta》2014,97(10):1406-1421
Earlier, it was found that the reaction of para‐mentha‐6,8‐diene‐2,3‐diol with 2,4,5‐trimethoxybenzaldehyde in the presence of Montmorillonite K 10 clay led to the formation of a compound with an unusual epoxychromene framework among other products. In the current work, systematic studies of the effect of the number and position of MeO groups in the aromatic ring of the aldehyde on the reaction route were performed to reveal the structural parameters, which favor the formation of compounds with an epoxychromene framework. Compounds with an epoxychromene framework were shown to be formed if the benzaldehyde contained MeO substituents in o‐ and p‐position. The highest yield was achieved in the case of 2,4,5‐trimethoxybenzaldehyde. 相似文献
37.
Anastasiya S. Sokolova Valentina P. Putilova Olga I. Yarovaya Anastasiya V. Zybkina Ekaterina D. Mordvinova Anna V. Zaykovskaya Dmitriy N. Shcherbakov Iana R. Orshanskaya Ekaterina O. Sinegubova Iana L. Esaulkova Sophia S. Borisevich Nikolay I. Bormotov Larisa N. Shishkina Vladimir V. Zarubaev Oleg V. Pyankov Rinat A. Maksyutov Nariman F. Salakhutdinov 《Molecules (Basel, Switzerland)》2021,26(8)
To date, the ‘one bug-one drug’ approach to antiviral drug development cannot effectively respond to the constant threat posed by an increasing diversity of viruses causing outbreaks of viral infections that turn out to be pathogenic for humans. Evidently, there is an urgent need for new strategies to develop efficient antiviral agents with broad-spectrum activities. In this paper, we identified camphene derivatives that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses, including influenza virus A/PR/8/34 (H1N1), Ebola virus (EBOV), and the Hantaan virus. The lead-compound 2a, with pyrrolidine cycle in its structure, displayed antiviral activity against influenza virus (IC50 = 45.3 µM), Ebola pseudotype viruses (IC50 = 0.12 µM), and authentic EBOV (IC50 = 18.3 µM), as well as against pseudoviruses with Hantaan virus Gn-Gc glycoprotein (IC50 = 9.1 µM). The results of antiviral activity studies using pseudotype viruses and molecular modeling suggest that surface proteins of the viruses required for the fusion process between viral and cellular membranes are the likely target of compound 2a. The key structural fragments responsible for efficient binding are the bicyclic natural framework and the nitrogen atom. These data encourage us to conduct further investigations using bicyclic monoterpenoids as a scaffold for the rational design of membrane-fusion targeting inhibitors. 相似文献
38.
The First Synthesis of (4S,5R,6R)‐5,6‐Dihydroxy‐4‐(prop‐1‐en‐2‐yl)cyclohex‐1‐ene‐1‐carboxylic Acid
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Oleg V. Ardashov Yuliya S. Demidova Dina V. Korchagina Konstantin P. Volcho Irina L. Simakova Nariman F. Salakhutdinov 《Helvetica chimica acta》2015,98(10):1442-1455
A putative acid metabolite of a novel highly effective antiparkinsonian agent, (4S,5R,6R)‐5,6‐dihydroxy‐4‐(prop‐1‐en‐2‐yl)cyclohex‐1‐ene‐1‐carboxylic acid ( 5 ), was synthesized for the first time. Several synthetic approaches based on different transformations of O‐bearing monoterpenoids of the pinane and p‐menthane series were developed and tested in the course of the study. Acid 5 was synthesized starting from a commercially available monoterpenoid, (?)‐verbenone, in a total yield of 4.4% over eight steps. 相似文献
39.
Nariman Ashrafi Abbas Hazbavi 《Archive of Applied Mechanics (Ingenieur Archiv)》2013,83(12):1739-1754
The rotational flow of viscoplastic fluids between concentric cylinders is examined while dissipation due to viscous effects through the energy balance. The viscosity of fluid is simultaneously dependent on shear rate and temperature. Exponential dependence of viscosity on temperature is modeled through Nahme law, and the shear dependency is modeled according to the Carreau equation. Hydrodynamically, stick boundary conditions are applied, and thermally, both constant temperature and constant heat flux on the exterior of cylinders are considered. The governing motion and energy balance equations are coupled adding complexity to the already highly correlated set of differential equations. Introduction of Nahme number has resulted in a nonlinear base flow between the cylinders. As well, the condition of constant heat flux has moved the point of maximum temperature toward the inner cylinder. Taking viscous heating into account, the effects of parameters such as Nahme and Brinkman numbers, material time and pseudoplasticity constant on the stability of the flow are investigated. Moreover, the study shows that the total entropy generation number decreases as the fluid elasticity increases. It, however, increases with increasing Nahme and Brinkman numbers. 相似文献
40.
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