Alibrary of novel spiro[pyrazole-4,5′-isoxazoline]-5-one derivatives were designed and synthesized using a concise and efficient one-pot reaction protocol through 1,3-dipolar cycloaddition between 4-benzylidene-3-met...Alibrary of novel spiro[pyrazole-4,5′-isoxazoline]-5-one derivatives were designed and synthesized using a concise and efficient one-pot reaction protocol through 1,3-dipolar cycloaddition between 4-benzylidene-3-methyl-1-phenyl-^(1)H-pyrazol-5(4H)-one and chlorooximes.The synthesized derivatives were elucidated and characterized based on their spectroscopic data,including infrared spectrometry(IR),^(1)H NMR,^(13)C NMR,and elemental and mass spectral analysis.The synthesized compounds were evaluated for their antitumor inhibition potency against four human cancer cell lines,including human prostatic adenocarcinoma(PC3),human colorectal carcinoma(HCT116),human liver hepatocellular carcinoma(HepG2)and breast adenocarcinoma(MCF7).The outcomes were compared with the standard reference drug Doxorubicin.Among the synthesized chlorooximes,compounds 6d and 6e were the most active compounds on all cell lines.The spiro[pyrazole-4,5′-isoxazoline]-5-one derivatives 7a and 7c were active on the HepG2 liver cancer cell line.In comparison,compounds 7f and 7g were moderately active on the MCF7 cell line.The structure-activity relationship was explored for the synthesized compounds.Besides,in silico analysis of physicochemical,adsorption,distribution,metabolism,excretion and toxicity(ADMET)properties were done to determine the potential capacity of drug candidates.Molecular docking study onto the epidermal growth factor(EGF)tyrosine kinase receptor(3POZ)was done for the most active compounds to validate the reliability of in vitro anticancer screenings.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
基金supported by the Fund of National Research Centre,Egypt.
文摘Alibrary of novel spiro[pyrazole-4,5′-isoxazoline]-5-one derivatives were designed and synthesized using a concise and efficient one-pot reaction protocol through 1,3-dipolar cycloaddition between 4-benzylidene-3-methyl-1-phenyl-^(1)H-pyrazol-5(4H)-one and chlorooximes.The synthesized derivatives were elucidated and characterized based on their spectroscopic data,including infrared spectrometry(IR),^(1)H NMR,^(13)C NMR,and elemental and mass spectral analysis.The synthesized compounds were evaluated for their antitumor inhibition potency against four human cancer cell lines,including human prostatic adenocarcinoma(PC3),human colorectal carcinoma(HCT116),human liver hepatocellular carcinoma(HepG2)and breast adenocarcinoma(MCF7).The outcomes were compared with the standard reference drug Doxorubicin.Among the synthesized chlorooximes,compounds 6d and 6e were the most active compounds on all cell lines.The spiro[pyrazole-4,5′-isoxazoline]-5-one derivatives 7a and 7c were active on the HepG2 liver cancer cell line.In comparison,compounds 7f and 7g were moderately active on the MCF7 cell line.The structure-activity relationship was explored for the synthesized compounds.Besides,in silico analysis of physicochemical,adsorption,distribution,metabolism,excretion and toxicity(ADMET)properties were done to determine the potential capacity of drug candidates.Molecular docking study onto the epidermal growth factor(EGF)tyrosine kinase receptor(3POZ)was done for the most active compounds to validate the reliability of in vitro anticancer screenings.
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.
