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Molecules ; 23(5)2018 May 05.
Article in English | MEDLINE | ID: mdl-29734741

ABSTRACT

A series of spirooxindolopyrrolidine fused N-styrylpiperidone heterocyclic hybrids has been synthesized in excellent yield via a domino multicomponent protocol that involves one-pot three component 1,3-dipolar cycloaddition and concomitant enamine reactions performed in an inexpensive ionic liquid, namely 1-butyl-3-methylimidazolium bromide ([bmim]Br). Compounds thus synthesized were evaluated for their cytotoxicity against U-937 tumor cells. Interestingly; compounds 5i and 5m exhibited a better cytotoxicity than the anticancer drug bleomycin. In addition; the effect of the synthesized compounds on the nuclear morphology of U937 FaDu cells revealed that treatment with compounds 5a⁻m led to their apoptotic cell death.


Subject(s)
Antineoplastic Agents/chemical synthesis , Indoles/chemical synthesis , Piperidones/chemical synthesis , Proto-Oncogene Proteins c-met/antagonists & inhibitors , Pyrrolidines/chemical synthesis , Spiro Compounds/chemical synthesis , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Binding Sites , Bleomycin/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Cycloaddition Reaction , Drug Design , Humans , Imidazoles/chemistry , Indoles/pharmacology , Inhibitory Concentration 50 , Lymphocytes/drug effects , Lymphocytes/pathology , Molecular Docking Simulation , Piperidones/pharmacology , Protein Binding , Protein Interaction Domains and Motifs , Protein Structure, Secondary , Proto-Oncogene Proteins c-met/chemistry , Proto-Oncogene Proteins c-met/metabolism , Pyrrolidines/pharmacology , Spiro Compounds/pharmacology , Structure-Activity Relationship
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