3,3-Diaryl-1,3-dihydroindol-2-ones as Antiproliferatives Mediated by Translation Initiation Inhibition

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 eIF2α. 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.