In vitro antiproliferative activity of glabridin derivatives and their in silico target identification

Abstract

Novel Mannich base derivatives of glabridin were synthesized and their antiproliferative activity were performed along with our previously reported glabridin-chalcone hybrids molecules (GCHMs) against various human cell lines MDA-MB-231 (breast adenocarcinoma), HEK-293 (embryonic kidney cell line), K562 (leukemia), MCF-7 (breast adenocarcinoma), HeLa (cervix adenocarcinoma), HepG2 (hepatocellular carcinoma) and WRL-68 (hepatic carcinoma). The result showed that the glabridin significantly reduced cell proliferation with IC₅₀ ranges from 3.67 to 58.30?µM against all the tested cell lines. The remarkable reduction in antiproliferative activity 2’,4’-dimethoxyglabridin and GCHMs compounds with phenolic OH groups protected by methoxy (OCH₃) groups suggested that the free OH groups are essential factor for the antiproliferative activity of glabridin and its derivatives. The Mannich base derivatives of glabridin showed moderate activity IC₅₀ (2.20–>95.78?µM). Furthermore, in silico target identification analysis revealed that AKT1, DECR1 and NOS1 are the potential targets for glabridin and their derivatives.     

Nickel(II) complexes bearing pyrazolylpyridines: synthesis,structures and ethylene oligomerization reactions

Reactions of 2‐bromo‐6‐(3,5‐dimethyl‐1H‐pyrazol‐1‐yl)pyridine ( L1 ) and 2,6‐bis(3,5‐dimethyl‐1H‐pyrazol‐1‐yl)pyridine ( L2 ) with NiCl₂ and NiBr₂ led to the formation of their respective metal complexes [NiCl₂(L1)] ( 1 ), [NiBr₂(L1)] ( 2 ) and [NiBr₂(L2)] ( 3 ) in moderate to high yields. The complexes were characterized using elemental analyses, mass spectrometry and single‐crystal X‐ray diffraction for 2 . The solid‐state structure of 2 confirmed the bidentate coordination mode of L1 and formation of a monometallic compound. Activation of the nickel(II) pre‐catalysts with methylaluminoxane afforded active catalysts in the ethylene oligomerization reaction to produce mainly butenes (84–86%). In contrast, activation of nickel(II) pre‐catalyst 2 with ethylaluminium dichloride resulted in partial Friedel–Crafts alkylation of the toluene solvent by the preformed oligomers. Complex structure, nature of co‐catalyst employed, type of solvent and reaction conditions influenced the catalytic behaviour of these pre‐catalysts. Copyright © 2015 John Wiley & Sons, Ltd.     

The influence of surface geometry and topography on the fatigue cracking behaviour of laser hybrid welded eccentric fillet joints

Laser hybrid welding of an eccentric fillet joint causes a complex geometry for fatigue load by 4-point bending. The weld surface geometry and topography were measured and studied in order to understand the crack initiation mechanisms. The crack initiation location and the crack propagation path were studied and compared to Finite Element stress analysis, taking into account the surface macro- and micro-geometry. It can be explained why the root and the upper weld toe are uncritical for cracking. The cracks that initiate from the weld bead show higher fatigue strength than the samples failing at the lower weld toe, as can be explained by a critical radius for the toe below which surface ripples instead determine the main stress raiser location for cracking. The location of maximum surface stress is related to a combination of throat depth, toe radius and sharp surface ripples along which the cracks preferably propagate.     

Kinetics and mechanism of the reaction of propylene oxide with chlorine atoms and hydroxy radicals

The kinetics and mechanism of gas‐phase propylene oxide (PPO) reactions were studied in a 142‐L reaction chamber by long‐path Fourier transform infrared spectroscopy at atmospheric pressure and 298 K. Rate coefficients for the reaction of PPO with ozone (O₃), chlorine atoms (Cl), and hydroxyl radicals (OH) were measured using the relative rate technique. Product yields of acetic acid, acetic formic anhydride, formic acid, and carbon monoxide were determined for the following reactions: PPO with Cl both in the presence and absence of NO, PPO with OH and NO, methyl acetate with Cl both in the presence and absence of NO, and ethyl formate with Cl both in the presence and absence of NO. The measured rate coefficients for PPO with O₃, Cl, and OH are <3.5 × 10^?21 cm³ molecule^?1 s^?1, (3.0 ± 0.7) × 10^?11 cm³ molecule^?1 s^?1, and (3.0 ± 1.0) × 10^?13 cm³ molecule^?1 s^?1, respectively. The carbon balance for the products measured ranged from 10% (for OH + PPO) to 100% (for Cl + methyl acetate in the absence of NO). The mechanistic and atmospheric implications of these measurements are discussed. © 2011 Wiley Periodicals, Inc. Int J Chem Kinet 43: 507–521, 2011     

Density waves and the effect of wall roughness in granular Poiseuille flow: Simulationand linear stability

The formation of density waves and the effect of wall roughness on them are studied using molecular dynamics simulations of gravity-driven granular Poiseuille flow. Three basic types of structures are found in moderately dense flows: a plug, a sinuous wave and a slug; a new varicose wave mode has been identified in dense flows with channels of large widths at moderate dissipations; only clump-like structures appear in dilute flows. The simulation results are contrasted with the predictions of a linear stability analysis of the kinetic-theory continuum equations for granular Poiseuille flow. The theoretical predictions on the form of density waves are in qualitative agreement with simulations in denser flows, however, there are discrepancies between simulation and theory in dilute flows.     

Study of reduction processes over cerium oxide surfaces with atomic hydrogen using ultra accelerated quantum chemical molecular dynamics

Ceria plays an important role in catalysis, due to its ability to store and release oxygen depending on the condition present in the catalyst environment. To analyze the role of ceria in catalytic reactions, it is necessary to know the details of the interaction of ceria surface with environmentally sensitive molecules. This study was conducted using ultra accelerated quantum chemical molecular dynamics. Its purpose was to investigate the reduction process of the (1 1 1) and (1 1 0) surfaces of ceria with atomic hydrogen as well as water desorption mechanisms from the surfaces. This simulation demonstrated that when a high-energy colliding hydrogen atoms are adsorbed on the ceria, it pulls up an O atom from the ceria surfaces and results in the formation of a H₂O molecule. This is the first dynamics simulation related to such reduction processes based on quantum chemistry.     

A sequential sampling rule for selecting the most probable multinomial event

Summary A sequential sampling rule is given for selecting the most probable event from a multinomial distribution withk cells. A random number of observations is taken from the given multinomial distribution at each stage of sampling, where the number is distributed according to a Poisson distribution with mean λ. The sampling is stopped when the count in any cell is greater than or equal to a given positive integerN. The cell with the highest count is selected for the most probable event. The mathematical analysis of the problem is simplified as a result of the statistical independence of the cell frequencies due to the randomization of the sample number. The expected value of the stage when the sampling terminates is decreasing in λ. The sequential sampling scheme in which one observation is taken at a time until the highest cell count is equal toN, corresponds to λ→0. A table is given showing some properties of the given selection procedure.     

Experimental investigation of the two-photon widths of the chi(c0) and the chi(c2) mesons

Using 12.7 fb(-1) of data collected with the CLEO detector at CESR, we observed two-photon production of the cc states chi(c0) and chi(c2) in their decay to pi(+)pi(-)pi(+)pi(-). We measured gamma(gammagamma)(chi(c))xB(chi(c)-->pi(+)pi(-)pi(+)pi(-)) to be 75+/-13(stat)+/-8(syst) eV for the chi(c0) and 6.4+/-1.8(stat)+/-0.8(syst) eV for the chi(c2), implying gamma(gammagamma)(chi(c0)) = 3.76+/-0.65(stat)+/-0.41(syst)+/-1.69(br) keV and gamma(gammagamma)(chi(c2)) = 0.53+/-0.15(stat)+/-0.06(syst)+/-0.22(br) keV. Also, cancellation of dominant experimental and theoretical uncertainties permits a precise comparison of gamma(gammagamma)(chi(c0))/gamma(gammagamma)(chi(c2)), evaluated to be 7.4+/-2.4(stat)+/-0.5(syst)+/-0.9(br), with QCD-based predictions.