title: 3,3-diaryl-1,3-dihydroindol-2-ones as antiproliferatives mediated by translation initiation inhibition.
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.
authors.affiliation: Laboratory for Translational Research, Harvard Medical School, One Kendall Square, Building 600, 3rd Floor, Cambridge, MA 02139, USA.
authors.forename: Amarnath
authors.initials: A
authors.lastname: Natarajan
authors.forename: Yun-Hua
authors.initials: YH
authors.lastname: Fan
authors.forename: Han
authors.initials: H
authors.lastname: Chen
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Guo
authors.forename: Julia
authors.initials: J
authors.lastname: Iyasere
authors.forename: Frederick
authors.initials: F
authors.lastname: Harbinski
authors.forename: William J
authors.initials: WJ
authors.lastname: Christ
authors.forename: Huseyin
authors.initials: H
authors.lastname: Aktas
authors.forename: Jose A
authors.initials: JA
authors.lastname: Halperin
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D015852:Eukaryotic Initiation Factor-2; D007211:Indoles; D002118:Calcium