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.
Forte, G., Fortuna, C., Salerno, L., Modica, M., Siracusa, M., Cardile, V., et al. (2013). Antitumor properties of substituted (αE)-α-(1H-indol-3-ylmethylene)benzeneacetic acids or amides. BIOORGANIC & MEDICINAL CHEMISTRY, 21(17), 5233-5245 [10.1016/j.bmc.2013.06.030].
Antitumor properties of substituted (αE)-α-(1H-indol-3-ylmethylene)benzeneacetic acids or amides
BULBARELLI, ALESSANDRA;LONATI, ELENA RITA;
2013
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.
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