A novel class of indole derivatives characterized by a (αE)-α-(1H-indol-3-ylmethylene)benzeneacetic acid or amide scaffold was synthesized. These derivatives, assayed for cell-growth inhibition activity against a panel of six different tumor cell lines, showed strong antiproliferative activity and selectivity mainly towards DU145 cell line. In particular, compounds 2d-m and 5 stand out for their cell growth inhibitory activity and, among them, compound 2d emerged for its selectivity towards DU145 with respect to other tested tumor cell lines. DU145 treated with 1 μM of 2d for 72 h showed p21Cip1 induction and suppression of Akt signaling together with induction of Rb. From a computational point of view, two different approaches were used in order to study topology and electronic properties of the novel compounds and to shed light on their drug-likeness properties. Firstly, topological and electronic features of the compounds endowed with the most relevant biological activity were deepened; in parallel, some ADME properties like solubility and permeability were predicted. © 2013 Elsevier Ltd. All rights reserved

Antitumor properties of substituted (alpha E)-alpha-(1H-indol-3-ylmethylene)benzeneacetic acids or amides

FORTE, GIUSEPPE;FORTUNA, COSIMO GIANLUCA;SALERNO, Loredana;MODICA, Maria Nunziata;SIRACUSA, Maria Angela;CARDILE, Venera;ROMEO, Giuseppe;PITTALA', Valeria
2013-01-01

Abstract

A novel class of indole derivatives characterized by a (αE)-α-(1H-indol-3-ylmethylene)benzeneacetic acid or amide scaffold was synthesized. These derivatives, assayed for cell-growth inhibition activity against a panel of six different tumor cell lines, showed strong antiproliferative activity and selectivity mainly towards DU145 cell line. In particular, compounds 2d-m and 5 stand out for their cell growth inhibitory activity and, among them, compound 2d emerged for its selectivity towards DU145 with respect to other tested tumor cell lines. DU145 treated with 1 μM of 2d for 72 h showed p21Cip1 induction and suppression of Akt signaling together with induction of Rb. From a computational point of view, two different approaches were used in order to study topology and electronic properties of the novel compounds and to shed light on their drug-likeness properties. Firstly, topological and electronic features of the compounds endowed with the most relevant biological activity were deepened; in parallel, some ADME properties like solubility and permeability were predicted. © 2013 Elsevier Ltd. All rights reserved
Prostate cancer, Indoles, Perkin-Oglialoro reaction, Retinoblastoma protein, p2lcio D1J145 cell line, DFT; VolSurf(+).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/57469
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