Abstract
A series of substituted 3,3-diphenyl-1,3-dihydro-indol-2-ones was synthesized from the corresponding isatins. The compounds were studied for cell growth inhibition mediated by partial depletion of intracellular Ca2+ stores that leads to phosphorylation of eIF2alpha. The diphenyloxindole (1) showed mechanism-specific antiproliferative activity that was comparable to known translation initiation inhibitors such as clotrimazole or troglitazone. SAR studies identified m'-tert-butyl and o-hydroxy substituted diphenyloxindole (25) as a lead compound for Ca2+-depletion-mediated inhibition of translation initiation.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Calcium / metabolism
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Cell Line
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Cell Line, Tumor
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Endoplasmic Reticulum / drug effects
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Endoplasmic Reticulum / metabolism
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Eukaryotic Initiation Factor-2 / metabolism
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Fluorescence Resonance Energy Transfer
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Humans
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Indoles / chemical synthesis*
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Indoles / chemistry
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Indoles / pharmacology
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Phosphorylation
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Protein Biosynthesis / drug effects
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Eukaryotic Initiation Factor-2
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Indoles
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Calcium