ABSTRACT
The discovery of a novel canine norovirus was recently reported. The VP1 capsid protein of this canine norovirus was expressed in Saccharomyces cerevisiae and purified with a yield of 1.6-1.8 mg/L. The yeast-expressed VP1 protein self-assembled into virus-like particles and exhibited antigenicity, proving to be suitable for serological assays.
Subject(s)
Capsid Proteins/biosynthesis , Capsid Proteins/isolation & purification , Gene Expression , Norovirus/genetics , Saccharomyces cerevisiae/genetics , Animals , Caliciviridae Infections/diagnosis , Caliciviridae Infections/veterinary , Caliciviridae Infections/virology , Capsid Proteins/genetics , Dog Diseases/diagnosis , Dog Diseases/virology , Dogs , Norovirus/metabolism , Saccharomyces cerevisiae/metabolismABSTRACT
Thirty-one 2'-hydroxychalcones were prepared via solid-phase synthesis by base-catalyzed aldol condensation of substituted 2'-hydroxyacetophenones and benzaldehydes. Chalcones were tested for their growth inhibitory activity in three human tumor cell lines (MCF-7, NCI-H460 and A375-C5) using the SRB assay. Results revealed that several of the tested compounds caused a pronounced dose-dependent growth inhibitory effect on the tumor cell lines studied in the low micromolar range. To gain further insight on the cellular mechanism of action of this class of compounds, studies of their effect on cell cycle profile as well as on induction of cellular apoptosis were also carried out. Generally, the tested chalcones interfered with the cell cycle profile and increased the percentage of apoptotic MCF-7 cells. The results here presented may help to identify new chalcone-like structures with optimized cell growth inhibitory activity which may be further tested as potential antitumor agents.
Subject(s)
Antineoplastic Agents/chemical synthesis , Chalcones/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis , Benzaldehydes/chemistry , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Chalcones/chemical synthesis , Chalcones/pharmacology , Drug Screening Assays, Antitumor , Humans , Solid-Phase Synthesis Techniques , Structure-Activity RelationshipABSTRACT
Some pyrazolo[3,4-d]pyrimidines, structurally related with allopurinol, a well known xanthine oxidase inhibitor, clinically used in the therapy of gout, have also been reported as potent inhibitors of xanthine oxidase and the growth of several human tumour cell lines. Considering the potential interest of this family of compounds, the aim of the present study was to synthesise and provide a full chemical characterization of new N-aryl-5-amino-4-cyanopyrazole derivatives and their corresponding pyrazolo[3,4-d]pyrimidines. Their biological activity pertaining to the xanthine oxidase inhibition and effect on the growth of three tumour cell lines (MCF-7, NCI-H460, and SF-268) are also provided. With only one exception, the synthesised compounds showed no effect on the growth of the three tumour cell lines. However, a strong xanthine oxidase inhibitory activity was observed for almost all pyrazolo[3,4-d]pyrimidines tested, revealing some of them IC(50) values below 1 microM. The results of the molecular docking studies of these compounds, against xanthine oxidoreductase are also described, providing an atomistic explanation of the differences in the inhibitory efficiency. MEP calculations were used to explain different inhibitory efficiency of similar inhibitors.
Subject(s)
Cell Proliferation/drug effects , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Nitriles/chemical synthesis , Nitriles/pharmacology , Pyrazoles/chemical synthesis , Pyrazoles/pharmacology , Xanthine Oxidase/antagonists & inhibitors , Allopurinol/chemistry , Humans , Models, Molecular , Molecular Structure , Structure-Activity Relationship , Tumor Cells, Cultured/drug effects , Xanthine Oxidase/metabolismABSTRACT
The synthesis of five new tetracyclic benzopsoralen analogues, compounds 2-6, with 9H-xanthen-9-one or 9H-carbazole frameworks, is described. Their inhibitory effects on the growth of three human tumor cell lines (MCF-7, SF-268, and NCI-460) were evaluated, and discussed in terms of structure-activity relationship, taking into account both geometric and electronic features. Generally, the angular compounds showed significant biological activities, but the arrangement of functional groups also contributed to the overall activity.
