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排序方式: 共有725条查询结果,搜索用时 15 毫秒
21.
Dmitry N. Kaluzhny Dr. Victor V. Tatarskiy Jr. Lyubov G. Dezhenkova Dr. Irina L. Plikhtyak Dr. Tatyana D. Miniker Dr. Anna K. Shchyolkina Dr. Sergey A. Strel'tsov Dr. Ghermes G. Chilov Dr. Fedor N. Novikov Dr. Irina Yu. Kubasova Dr. Zoya S. Smirnova Dr. Stalina Ya. Mel'nik Dr. Mikhail A. Livshits Dr. Olga F. Borisova Dr. Alexander A. Shtil Dr. 《ChemMedChem》2009,4(10):1641-1648
Novel indolocarbazole derivative 12‐(α‐L ‐arabinopyranosyl)indolo[2,3‐α]pyrrolo[3,4‐c]carbazole‐5,7‐dione (AIC) demonstrated high potency (at submicromolar concentrations) against the NCI panel of human tumor cell lines and transplanted tumors in vivo. In search of tentative targets for AIC, we found that the drug formed high affinity intercalative complexes with d(AT)20, d(GC)20 and calf thymus DNA (binding constants (1.6×106) M ?1≤Ka≤(3.3×106) M ?1). The drug intercalated preferentially into GC pairs of the duplex. Importantly, the concentrations at which AIC formed the intercalative complexes with DNA (C≤1 μM ) were identical to the concentrations that triggered p53‐dependent gene reporter transactivation, the replication block, the inhibition of topoisomerase I‐mediated DNA relaxation and death of HCT116 human colon carcinoma cells. We conclude that the formation of high affinity intercalative complexes with DNA is an important factor for anticancer efficacy of AIC. 相似文献
22.
Oxana Kazakova Irina Smirnova Elena Tretyakova Ren Csuk Sophie Hoenke Lucie Fischer 《International journal of molecular sciences》2021,22(4)
Semi-synthetic triterpenoids, holding an amino substituted seven-membered A-ring (azepano-ring), which could be synthesized from triterpenic oximes through a Beckmann type rearrangement followed by a reduction of lactame fragment, are considered to be novel promising agents exhibiting anti-microbial, alpha-glucosidase, and butyrylcholinesterase inhibitory activities. In this study, in an attempt to develop new antitumor candidates, a series of A-ring azepano- and 3-amino-3,4-seco-derivatives of betulin, oleanolic, ursolic, and glycyrrhetinic acids were evaluated for their cytotoxic activity against five human cancer cell lines and non-malignant mouse fibroblasts by means of a colorimetric sulforhodamine assay. Azepanoallobetulinic acid amide derivative 11 was the most cytotoxic compound of this series but showed little selectivity between the different human tumor cell lines. Flow cytometry experiments showed compound 11 to act mainly by apoptosis (44.3%) and late apoptosis (21.4%). The compounds were further screened at the National Cancer Institute towards a panel of 60 cancer cell lines. It was found that compounds 3, 4, 7, 8, 9, 11, 15, 16, 19, and 20 showed growth inhibitory (GI50) against the most sensitive cell lines at submicromolar concentrations (0.20–0.94 μM), and their cytotoxic activity (LC50) was also high (1–6 μM). Derivatives 3, 8, 11, 15, and 16 demonstrated a certain selectivity profile at GI50 level from 5.16 to 9.56 towards K-562, CCRF-CEM, HL-60(TB), and RPMI-8226 (Leukemia), HT29 (Colon cancer), and OVCAR-4 (Ovarian cancer) cell lines. Selectivity indexes of azepanoerythrodiol 3 at TGI level ranged from 5.93 (CNS cancer cell lines SF-539, SNB-19 and SNB-75) to 14.89 for HCT-116 (colon cancer) with SI 9.56 at GI50 level for the leukemia cell line K-562. The present study highlighted the importance of A-azepano-ring in the triterpenic core for the development of novel antitumor agents, and a future aim to increase the selectivity profile will thus lie in the area of modifications of azepano-triterpenic acids at their carboxyl group. 相似文献
23.
Alsu Z. Malikova Anastasia S. Shcherbakova Konstantin A. Konduktorov Anastasia S. Zemskaya Alexandra A. Dalina Vladimir I. Popenko Olga G. Leonova Alexei V. Morozov Nikolay N. Kurochkin Olga A. Smirnova Sergey N. Kochetkov Maxim V. Kozlov 《International journal of molecular sciences》2021,22(9)
Recent evidence suggests that fibrotic liver injury in patients with chronic hepatitis C correlates with cellular senescence in damaged liver tissue. However, it is still unclear how senescence can affect replication of the hepatitis C virus (HCV). In this work, we report that an inhibitor of cyclin-dependent kinases 4/6, palbociclib, not only induced in hepatoma cells a pre-senescent cellular phenotype, including G1 arrest in the cell cycle, but also accelerated viral replicon multiplication. Importantly, suppression of HCV replication by direct acting antivirals (DAAs) was barely affected by pre-senescence induction, and vice versa, the antiviral activities of host-targeting agents (HTAs), such as inhibitors of human histone deacetylases (HDACi), produced a wide range of reactions—from a dramatic reduction to a noticeable increase. It is very likely that under conditions of the G1 arrest in the cell cycle, HDACi exhibit their actual antiviral potency, since their inherent anticancer activity that complicates the interpretation of test results is minimized. 相似文献
24.
Yana Y. Toporkova Elena O. Smirnova Natalia V. Lantsova Lucia S. Mukhtarova Alexander N. Grechkin 《International journal of molecular sciences》2021,22(9)
The CYP74 clan cytochromes (P450) are key enzymes of oxidative metabolism of polyunsaturated fatty acids in plants, some Proteobacteria, brown and green algae, and Metazoa. The CYP74 enzymes, including the allene oxide synthases (AOSs), hydroperoxide lyases, divinyl ether synthases, and epoxyalcohol synthases (EASs) transform the fatty acid hydroperoxides to bioactive oxylipins. A novel CYP74 clan enzyme CYP440A18 of the Asian (Belcher’s) lancelet (Branchiostoma belcheri, Chordata) was biochemically characterized in the present work. The recombinant CYP440A18 enzyme was active towards all substrates used: linoleate and α-linolenate 9- and 13-hydroperoxides, as well as with eicosatetraenoate and eicosapentaenoate 15-hydroperoxides. The enzyme specifically converted α-linolenate 13-hydroperoxide (13-HPOT) to the oxiranyl carbinol (9Z,11R,12R,13S,15Z)-11-hydroxy-12,13-epoxy-9,15-octadecadienoic acid (EAS product), α-ketol, 12-oxo-13-hydroxy-9,15-octadecadienoic acid (AOS product), and cis-12-oxo-10,15-phytodienoic acid (AOS product) at a ratio of around 35:5:1. Other hydroperoxides were converted by this enzyme to the analogous products. In contrast to other substrates, the 13-HPOT and 15-HPEPE yielded higher proportions of α-ketols, as well as the small amounts of cyclopentenones, cis-12-oxo-10,15-phytodienoic acid and its higher homologue, dihomo-cis-12-oxo-3,6,10,15-phytotetraenoic acid, respectively. Thus, the CYP440A18 enzyme exhibited dual EAS/AOS activity. The obtained results allowed us to ascribe a name “B. belcheri EAS/AOS” (BbEAS/AOS) to this enzyme. BbEAS/AOS is a first CYP74 clan enzyme of Chordata species possessing AOS activity. 相似文献
25.
The results of theoretical and experimental investigation of the average dynamics of inhomogeneous systems in rotating cavity
in the presence of oscillating force field are highlighted and analyzed. Average behavior of nonisothermal liquid as well
as different multiphase systems (two liquids, liquid and gas, solid in liquid, granular matter in liquid) in quickly rotating
horizontal cylinder subjected to vibrations of different direction is described. The specificity of dynamics of all the systems
is determined by the Coriolis force which defines not only the average flows but the fluid oscillations also. The resonant
excitation of inertial oscillations of liquid results in generation of intensive mean flows. The structure of vibrational
streams is essentially determined by the type of inertial waves. So, excitation of an azimuthal wave generates azimuthal streams
(outrunning or lagging, depending on frequency of the wave), three-dimensional standing waves (in the systems with deformable
interface) generate regular spatial flows of high intensity. Under the resonant conditions the influence of vibrations appears
to be very strong, the speed of mean streaming can achieve the values comparable with the speed of rotation of the container. 相似文献
26.
M. S. Smirnov O. V. Ovchinnikov A. N. Latyshev A. M. Smirnova P. V. Novikov M. A. Efimova 《Semiconductors》2009,43(7):852-857
In the AgCl microcrystals with adsorbed methylene blue dye molecules, sensitized anti-Stokes luminescence centers formed as a result of a photostimulated low-temperature (77 K) process are observed. The emission is recorded on excitation of the samples by radiation with the flux density 1014?1015 photon cm?2 s?1 in the spectral range 620–750 nm corresponding to optical absorption in the adsorbed dye molecules and adsorbed Ag1, Ag2, and Ag3 clusters. It is shown that the anti-Stokes luminescence centers formed by photo-stimulation present (adsorbed dye molecule)—(silver subnanocluster) hybrid nanostructures, in which the bonding between the components is weak but sufficient to provide the possibility for two-photon interband transitions that occur due to transfer of the electron’s excitation energy from the dye molecule to the silver cluster with subsequent photoionization of the cluster. 相似文献
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