Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a promising target for anticancer therapy due to its ability to counter the effects topoisomerase 1 (Top1) poison, such as topotecan, thus, decreasing their efficacy. Compounds containing adamantane and monoterpenoid residues connected via 1,2,4-triazole or 1,3,4-thiadiazole linkers were synthesized and tested against Tdp1. All the derivatives exhibited inhibition at low micromolar or nanomolar concentrations with the most potent inhibitors having IC50 values in the 0.35–0.57 µM range. The cytotoxicity was determined in the HeLa, HCT-116 and SW837 cancer cell lines; moderate CC50 (µM) values were seen from the mid-teens to no effect at 100 µM. Furthermore, citral derivative 20c, α-pinene-derived compounds 20f, 20g and 25c, and the citronellic acid derivative 25b were found to have a sensitizing effect in conjunction with topotecan in the HeLa cervical cancer and colon adenocarcinoma HCT-116 cell lines. The ligands are predicted to bind in the catalytic pocket of Tdp1 and have favorable physicochemical properties for further development as a potential adjunct therapy with Top1 poisons. 相似文献
Chemistry of Heterocyclic Compounds - A number of novel amides were synthesized by coupling of 6-[(9H-purin-6-yl)amino]hexanoic acid to heterocyclic amines. The antiviral activity of the obtained... 相似文献
Journal of Radioanalytical and Nuclear Chemistry - Thin natEr2O3 targets were irradiated on cyclotron by 60 MeV alpha particles. Thulium and ytterbium radioisotopes, formed during... 相似文献
Transport properties of perovskite-type Sr11Mo4O23 and composite Sr11Mo4O23 - 1 wt% Al2O3 were studied at 400–1300 K in the oxygen partial pressure range from 0.21 down to 10−19 atm. The electromotive force and faradaic efficiency measurements, in combination with the energy-dispersive spectroscopy of the fractured electrochemical cells, unambiguously showed prevailing role of the oxygen ionic conductivity under oxidizing conditions. At temperatures above 600 K, protonic and cationic transport can be neglected. The oxygen ion transference numbers vary in the range of 0.95–1.00 at 973–1223 K. At temperatures lower than 550 K, the total conductivity of Sr11Mo4O23 - 1 wt% Al2O3 composite measured by impedance spectroscopy tends to increase in wet atmospheres, thus indicating that hydration and protonic transport become significant. Reducing oxygen partial pressure below 10−10–10−9 atm leads to a significant increase in the n-type electronic conduction. The average thermal expansion coefficients in oxidizing atmospheres are (14.3–15.0) × 10−6 K−1 at 340–740 K and (18.3–19.2) × 10−6 K−1 at 870–1370 K.
Journal of Thermal Analysis and Calorimetry - The derivative of 1,2,4-thiadiazole (TDZ) can be considered as a perspective agent for the Alzheimer’s disease prevention. Due to a highly... 相似文献
Journal of Thermal Analysis and Calorimetry - The bitumen-containing reservoir rocks taken from Devonian terrigenous formation of Romashkino and Bavly oil fields (Russia) were sampled and... 相似文献
Spruce (Piceaabies) wood hemicelluloses have been obtained by the noncatalytic and catalytic oxidative delignification in the acetic acid-water-hydrogen peroxide medium in a processing time of 3–4 h and temperatures of 90–100 °C. In the catalytic process, the H2SO4, MnSO4, TiO2, and (NH4)6Mo7O24 catalysts have been used. A polysaccharide yield of up to 11.7 wt% has been found. The hemicellulose composition and structure have been studied by a complex of physicochemical methods, including gas and gel permeation chromatography, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. The galactose:mannose:glucose:arabinose:xylose monomeric units in a ratio of 5:3:2:1:1 have been identified in the hemicelluloses by gas chromatography. Using gel permeation chromatography, the weight average molar mass Mw of hemicelluloses has been found to attain 47,654 g/mol in noncatalytic delignification and up to 42,793 g/mol in catalytic delignification. Based on the same technique, a method for determining the α and k parameters of the Mark–Kuhn–Houwink equation for hemicelluloses has been developed; it has been established that these parameters change between 0.33–1.01 and 1.57–472.17, respectively, depending on the catalyst concentration and process temperature and time. Moreover, the FTIR spectra of the hemicellulose samples contain all the bands characteristic of heteropolysaccharides, specifically, 1069 cm−1 (C–O–C and C–O–H), 1738 cm−1 (ester C=O), 1375 cm−1 (–C–CH3), 1243 cm−1 (–C–O–), etc. It has been determined by the thermogravimetric analysis that the hemicelluloses isolated from spruce wood are resistant to heating to temperatures of up to ~100 °C and, upon further heating, start destructing at an increasing rate. The antioxidant activity of the hemicelluloses has been examined using the compounds simulating the 2,2-diphenyl-2-picrylhydrazyl free radicals. 相似文献
Velocities of propagation of elastic waves along principal crystallographic directions in Hg2Br2 and Hg2J2 single crystals were measured using the pulse and phase-pulse techniques. The values obtained were used to calculate the components of the elastic tensors cik and sik, as well as the phase and group velocities of propagation of longitudinal and transverse waves in the (100) and (001) planes, and the angular deviation of acoustic energy flux from the direction of the corresponding wave normal. Knowledge of the anisotropy of the elastic properties of Hg2X2 crystals and of their change with the anion (X = Cl, Br, J) leads to deeper understanding of the character of bonds in the crystal lattice and points the way to a better utilization of technical properties of the crystals. — Minimum velocity of propagation of an elastic wave falls in the case of Hg2J2 to a value v [100] [11 10] = 0,25 · 105 cm/s, what is the lowest value known among all crystals. Maximum angular deviation of acoustic energy flux — nearly 50° — is exhibited by the quasi-longitudinal wave in Hg2J2 crystals. On substituting the Cl− ions with Br− and J− ions, the anisotropy of elastic moduli C33/C11 increases by nearly 80%. Different mechanisms contribute to vectorial dependence of the elastic properties along different crystallographic directions. 相似文献