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.

Synthesis, Characterization and Docking Studies of 4, 4’-Diaminotriphenylmethanes (DATPMs)

“…The mode of action of this triarylmethyl motif underlies in its ability to inhibit translation mediated by depletion of intracellular Ca +2 concentrations and also by inhibition of glycolysis by prompting the detachment of mitochondrial bound hexokinase [3,5]. 3,3-diaryl-1,3-dihyroindoles, an indole modified triarylmethanes, possess antiproliferative activity against cancer cell lines in cell culture [6,7]. Previously, Triarylmethanes (TAMs) have been found to be potent against digestive and intestinal parasitic worms and other protozoa like filariae, trichomonads, and trypanosomes [8].…”

An efficient synthesis of bis-indolyloxindoles from (phenylimino)indolin-2-ones and 1H-indole catalyzed by Citric acid

“…Especially, 3, 3-diaryloxindoles are known to possess mechanism-specific antibacterial, antiprotozoal, antiproliferative, and antiinflammatory activities [9]. These compounds have also been used as laxatives [10] and lead compounds for Ca2C-depletion mediated inhibition of translation initiation [11]. The parent compound, trisindoline is a natural product and has been isolated by Kabayshi et al [12].…”

Tungstic acid-catalyzed synthesis of 3,3-bis (1H-indol-3-yl)indolin-2-one derivatives

“…Among biologically active heterocyclic compounds [1][2][3], derivatives of oxindole [3,3-bis(1H-indol-3-yl) indolin-2-one, 3a in Scheme 1) attract much attention as antiinflammatory [4], anti-HIV [5], and antitumor [6] agents, among other things [7,8]. Oxindole is also an integral component of many natural products including convolutamydines [9], arundaphine [10], donaxaridine [11], paratunamide [12], and maremycins [13].…”