Targeted therapies are gaining global attention to tackle Renal Cancer(RC).This study aims to screen FPMXY-14(novel arylidene analogue)for Akt inhibition by computational and in vitro methods.FPMXY-14 was subjected to...Targeted therapies are gaining global attention to tackle Renal Cancer(RC).This study aims to screen FPMXY-14(novel arylidene analogue)for Akt inhibition by computational and in vitro methods.FPMXY-14 was subjected to proton NMR analysis and Mass spectrum analysis.Vero,HEK-293,Caki-1,and A498 cell lines were used.Akt enzyme inhibition was studied with the fluorescent-based kit assay.Modeller 9.19,Schrodinger 2018-1,LigPrep module,and Glide docking were used in computational analysis.The nuclear status was assessed by PI/Hoechst-333258 staining,cell cycle,and apoptosis assays were performed using flow cytometry.Scratch wound and migrations assays were performed.Western blotting was applied to study key signalling proteins.FPMXY-14 selectively inhibited kidney cancer cell proliferation with GI50 values of 77.5 nM and 101.40 nM in Caki-1 cells and A-498 cells,respectively.The compound dose-dependently inhibited Akt enzyme with an IC50 value of 148.5 nM and bound efficiently at the allosteric pocking of the Akt when computationally analyzed.FPMXY-14 caused nuclear condensation/fragmentation,increased the sub G_(0)/G_(1),G_(2)M populations,and induced early,late phase apoptosis in both cells when compared to controls.Treatment of the compound inhibited wound healing and migration of tumor cells,while proteins like Bcl-2,Bax,and caspase 3 were also altered.FPMXY-14 effectively inhibited the phosphorylation of Akt in these cancer cells,while total Akt was unaltered.FPMXY-14 exhibited anti-proliferative and anti-metastatic activities in kidney cancer cells by attenuating the Akt enzyme.Further pre-clinical research on animals with a detailed pathway elucidation is recommended.展开更多
A fast, high efficiency and environmentally friendly procedure for the synthesis of 2-aryl benzim-idazole derivatives has been reported. Reaction between 1,2-phenylenediamine derivatives and arylidene malononitrile un...A fast, high efficiency and environmentally friendly procedure for the synthesis of 2-aryl benzim-idazole derivatives has been reported. Reaction between 1,2-phenylenediamine derivatives and arylidene malononitrile under aqueous media and also solvent-free conditions generates 2-aryl benzimidazole derivatives with a high yield.展开更多
An efficient and facile approach for tetrachlorosilane as an in situ mediated transformation via a one-pot, synthesis of vicinal bromoazides through the generation of BrN3 from azidochlorosilane and N-bromosuccinimide...An efficient and facile approach for tetrachlorosilane as an in situ mediated transformation via a one-pot, synthesis of vicinal bromoazides through the generation of BrN3 from azidochlorosilane and N-bromosuccinimide in acetonitrile as solvent at ambient temperature is achieved. This catalytic process represents a highly regioselective and high yielding method for the synthesis of 1,2- bromoazides. Thiamine pyrophosphate （TPP） riboswitches regulate essential genes in bacteria by changing conformation upon binding intracellular TPP. Molecular docking studies are conducted to understand the orientation and the interaction of each synthesized molecules with TPP riboswitches, 2016 Chinese Chemical Society and Institute of Materia Medica, Chinese Academv of Medical Sciences.展开更多
A coprecipitation method was used to synthesize superparamagnetic CoFe2O4 nanoparticles without using any capping agents/surfactants. The prepared nanoparticles were characterized using Fourier transform infrared spec...A coprecipitation method was used to synthesize superparamagnetic CoFe2O4 nanoparticles without using any capping agents/surfactants. The prepared nanoparticles were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, X-ray diffraction, a vibrating sample magnetometer (VSM), N2 adsorption and thermogravimetric/differential thermal analysis/differential thermal gravimetry techniques. The synthesized spinel CoFe2O4 nanoparticles had an average size of 2-8 nm with a high surface area (140.9 m2/g). The field-dependent magnetization, demonstrated by VSM and saturation magnetization, was found to be 1.77 emu/g. An efficient method was used for the synthesis of arylidene barbituric acid derivatives using CoFe2O4 magnetic nanoparticles as a magnetically separable and reusable catalyst in aqueous ethanol. The attractive features of this synthetic protocol were very short reaction time, high yields, high turnover frequency, simple work-up procedure, economy, a clean reaction methodology, and chemoselectivity, as well as provision of an ecofriendly and green synthesis.展开更多
A series of 5-arylidene thiobarbituric acids were prepared from aromatic aldehydes and thiobarbituric acid in water without catalyst conditions in good yields. The structures were characterized by elemental analysis,...A series of 5-arylidene thiobarbituric acids were prepared from aromatic aldehydes and thiobarbituric acid in water without catalyst conditions in good yields. The structures were characterized by elemental analysis, IR and 1H NMR spectra.展开更多
基金supported by the Deanship of Scientific Research at King Khalid University,Abha,Saudi Arabia,for funding this work through the General Research Project under Grant No. (G.R.P.1/39/39).
文摘Targeted therapies are gaining global attention to tackle Renal Cancer(RC).This study aims to screen FPMXY-14(novel arylidene analogue)for Akt inhibition by computational and in vitro methods.FPMXY-14 was subjected to proton NMR analysis and Mass spectrum analysis.Vero,HEK-293,Caki-1,and A498 cell lines were used.Akt enzyme inhibition was studied with the fluorescent-based kit assay.Modeller 9.19,Schrodinger 2018-1,LigPrep module,and Glide docking were used in computational analysis.The nuclear status was assessed by PI/Hoechst-333258 staining,cell cycle,and apoptosis assays were performed using flow cytometry.Scratch wound and migrations assays were performed.Western blotting was applied to study key signalling proteins.FPMXY-14 selectively inhibited kidney cancer cell proliferation with GI50 values of 77.5 nM and 101.40 nM in Caki-1 cells and A-498 cells,respectively.The compound dose-dependently inhibited Akt enzyme with an IC50 value of 148.5 nM and bound efficiently at the allosteric pocking of the Akt when computationally analyzed.FPMXY-14 caused nuclear condensation/fragmentation,increased the sub G_(0)/G_(1),G_(2)M populations,and induced early,late phase apoptosis in both cells when compared to controls.Treatment of the compound inhibited wound healing and migration of tumor cells,while proteins like Bcl-2,Bax,and caspase 3 were also altered.FPMXY-14 effectively inhibited the phosphorylation of Akt in these cancer cells,while total Akt was unaltered.FPMXY-14 exhibited anti-proliferative and anti-metastatic activities in kidney cancer cells by attenuating the Akt enzyme.Further pre-clinical research on animals with a detailed pathway elucidation is recommended.
文摘A fast, high efficiency and environmentally friendly procedure for the synthesis of 2-aryl benzim-idazole derivatives has been reported. Reaction between 1,2-phenylenediamine derivatives and arylidene malononitrile under aqueous media and also solvent-free conditions generates 2-aryl benzimidazole derivatives with a high yield.
文摘An efficient and facile approach for tetrachlorosilane as an in situ mediated transformation via a one-pot, synthesis of vicinal bromoazides through the generation of BrN3 from azidochlorosilane and N-bromosuccinimide in acetonitrile as solvent at ambient temperature is achieved. This catalytic process represents a highly regioselective and high yielding method for the synthesis of 1,2- bromoazides. Thiamine pyrophosphate （TPP） riboswitches regulate essential genes in bacteria by changing conformation upon binding intracellular TPP. Molecular docking studies are conducted to understand the orientation and the interaction of each synthesized molecules with TPP riboswitches, 2016 Chinese Chemical Society and Institute of Materia Medica, Chinese Academv of Medical Sciences.
文摘A coprecipitation method was used to synthesize superparamagnetic CoFe2O4 nanoparticles without using any capping agents/surfactants. The prepared nanoparticles were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, X-ray diffraction, a vibrating sample magnetometer (VSM), N2 adsorption and thermogravimetric/differential thermal analysis/differential thermal gravimetry techniques. The synthesized spinel CoFe2O4 nanoparticles had an average size of 2-8 nm with a high surface area (140.9 m2/g). The field-dependent magnetization, demonstrated by VSM and saturation magnetization, was found to be 1.77 emu/g. An efficient method was used for the synthesis of arylidene barbituric acid derivatives using CoFe2O4 magnetic nanoparticles as a magnetically separable and reusable catalyst in aqueous ethanol. The attractive features of this synthetic protocol were very short reaction time, high yields, high turnover frequency, simple work-up procedure, economy, a clean reaction methodology, and chemoselectivity, as well as provision of an ecofriendly and green synthesis.
基金the Natural Science Foundation of Shaan’xi Province(No.2000H03)for support of this work.
文摘A series of 5-arylidene thiobarbituric acids were prepared from aromatic aldehydes and thiobarbituric acid in water without catalyst conditions in good yields. The structures were characterized by elemental analysis, IR and 1H NMR spectra.
