ABSTRACT
We report an efficient method for asymmetric synthesis of chiral oxindoles. Allyl palladium(II) chloride dimer (APC)-catalyzed, in combination with ß-isocupreidine (ß-ICD)-cocatalyzed, reaction of diazoacetamide with Morita-Baylis-Hillman (MBH) carbonates proves to be a facile protocol to access multifunctional oxindoles bearing a C-3 quaternary stereo center. This tandem reaction tolerates a wide variety of functional groups on the both aromatic rings. This method delivers a variety of chiral oxindoles in 50-75% yield and with up to 95:5 dr in most cases along with up to 93:7 er.
ABSTRACT
A new series of biquinoline-pyridine hybrids were designed and synthesized by a base-catalyzed cyclocondensation through one-pot multicomponent reaction. All compounds were tested for in vitro anticancer activities against two cancer cell lines A549 (adenocarcinomic human alveolar basal epithelial) and Hep G2 (liver cancer). Enzyme inhibitory activities of all compounds were carried out against EGFR and HER-2 kinase. Of the compounds studied, majority of the compounds showed effective anticancer activity against used cancer cell lines. Compound 9i (IC50=0.09 µM) against EGFR and (IC50=0.2 µM) against HER-2 kinase displayed the most potent inhibitory activity as compared to other member of the series. In the molecular modelling study, compound 9i was bound in to the active pocket of EGFR with four hydrogen bonds and two π-cation interactions having minimum binding energy ΔGb=-54.4 kcal/mol.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Design , ErbB Receptors/antagonists & inhibitors , Protein Kinase Inhibitors/pharmacology , Pyridines/pharmacology , Quinolines/pharmacology , Receptor, ErbB-2/antagonists & inhibitors , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , ErbB Receptors/metabolism , Hep G2 Cells , Humans , Models, Molecular , Molecular Structure , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Pyridines/chemistry , Quinolines/chemistry , Receptor, ErbB-2/metabolism , Structure-Activity RelationshipABSTRACT
A series of 2-styryl-5-nitroimidazole derivatives containing 1,4-benzodioxan moiety (3a-3r) has been designed, synthesized and their biological activities were also evaluated as potential antiproliferation and focal adhesion kinase (FAK) inhibitors. Among all the compounds, 3p showed the most potent activity in vitro which inhibited the growth of A549 with IC50 value of 3.11 µM and Hela with IC50 value of 2.54 µM respectively. Compound 3p also exhibited significant FAK inhibitory activity (IC50=0.45 µM). Docking simulation was performed for compound 3p into the FAK structure active site to determine the probable binding model.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Dioxanes/chemistry , Focal Adhesion Protein-Tyrosine Kinases/antagonists & inhibitors , Molecular Docking Simulation , Nitroimidazoles/pharmacology , Protein Kinase Inhibitors/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Focal Adhesion Protein-Tyrosine Kinases/metabolism , HeLa Cells , Humans , Molecular Structure , Nitroimidazoles/chemical synthesis , Nitroimidazoles/chemistry , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Structure-Activity RelationshipABSTRACT
A new series of 32 derivatives of 4-pyrazolyl-N-(hetero)arylquinoline 5a-p and 6a-p were synthesized by a one-pot base-catalyzed cyclocondensation reaction of 1-phenyl-3-(hetero)aryl-pyrazole-4-carbaldehyde 1a-h, malononitrile 2, and 3-(hetero)aryl-5,5-disubstitutedcyclohex-2-enone 3a-b or 4a-b, respectively. All the synthesized compounds were characterized by elemental analysis, FT-IR, (1) H-NMR, and (13) C-NMR spectral data. All the synthesized compounds were screened, against six bacterial pathogens, namely Bacillus subtilis, Clostridium tetani, Streptococcus pneumoniae, Salmonella typhi, Vibrio cholerae, Escherichia coli, and antifungal activity, against two fungal pathogens Aspergillus fumigatus and Candida albicans, using broth microdilution MIC method. Some of the compounds were found to be more or equipotent against most of the employed strains than commercially available drugs as evident from the screening data.
Subject(s)
Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/pharmacology , Microbial Sensitivity Tests/methods , Pyrazoles/chemistry , Quinolines/chemical synthesis , Quinolines/pharmacology , Anti-Infective Agents/chemistry , In Vitro Techniques , Molecular Structure , Quinolines/chemistry , Structure-Activity RelationshipABSTRACT
A new series of 12 derivatives of 4-pyrazolyl-N-arylquinoline-2,5-dione (4a-l) were synthesized by one pot base catalyzed cyclocondensation reaction of 1-aryl-5-chloro-3-methyl-1H-pyrazole-4-carbaldehyde (1a-c), Meldrum's acid (2) and 3-arylamino-5,5-disubstitutedcyclohex-2-enone (3a-d). All the compounds were characterized by elemental analysis, FT-IR, (1)H NMR and (13)C NMR spectral data and were screened, against six bacterial pathogens, namely Bacillus subtilis, Clostridium tetani, Streptococcus pneumoniae, Salmonella typhi, Vibrio cholerae, Escherichia coli and antifungal activity, against two fungal pathogens Aspergillus fumigatus and Candida albicans, using broth microdilution MIC (minimum inhibitory concentration) method. Some of the compounds were found to be equipotent or more potent than commercial drugs, against most of the employed strains, as evident from the screening data.
