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.
Keywords:
1,3-dipolar cycloaddition; cytotoxicity assays; domino reaction; ionic liquids; molecular docking.
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Binding Sites
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Bleomycin / pharmacology
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Cell Line, Tumor
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Cell Survival / drug effects
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Cycloaddition Reaction
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Drug Design
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Humans
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Imidazoles / chemistry
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Indoles / chemical synthesis*
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Indoles / pharmacology
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Inhibitory Concentration 50
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Lymphocytes / drug effects
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Lymphocytes / pathology
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Molecular Docking Simulation
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Piperidones / chemical synthesis*
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Piperidones / pharmacology
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Protein Binding
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Protein Interaction Domains and Motifs
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Protein Structure, Secondary
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Proto-Oncogene Proteins c-met / antagonists & inhibitors*
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Proto-Oncogene Proteins c-met / chemistry
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Proto-Oncogene Proteins c-met / metabolism
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Pyrrolidines / chemical synthesis*
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Pyrrolidines / pharmacology
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Spiro Compounds / chemical synthesis*
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Spiro Compounds / pharmacology
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Imidazoles
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Indoles
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Piperidones
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Pyrrolidines
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Spiro Compounds
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Bleomycin
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1-butyl-3-methylimidazolium chloride
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MET protein, human
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Proto-Oncogene Proteins c-met