Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 47, Issue 8, Pages 1882-1885Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm0499716
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- NCI NIH HHS [5U19 CA 87427] Funding Source: Medline
- NIA NIH HHS [R21 AG032546] Funding Source: Medline
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A series of substituted 3,3-diphenyl-1,3-dihydroindol-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.
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