title: Antitumor properties of substituted (αE)-α-(1H-indol-3-ylmethylene)benzeneacetic acids or amides.
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 1μM of 2d for 72h showed p21(Cip1) 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.
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi di Catania, viale A. Doria 6, 95125 Catania, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Forte
authors.forename: Cosimo Gianluca
authors.initials: CG
authors.lastname: Fortuna
authors.forename: Loredana
authors.initials: L
authors.lastname: Salerno
authors.forename: Maria N
authors.initials: MN
authors.lastname: Modica
authors.forename: Maria A
authors.initials: MA
authors.lastname: Siracusa
authors.forename: Venera
authors.initials: V
authors.lastname: Cardile
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Romeo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bulbarelli
authors.forename: Elena
authors.initials: E
authors.lastname: Lonati
authors.forename: Valeria
authors.initials: V
authors.lastname: Pittalà
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006207:Half-Life; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D008968:Molecular Conformation; D010648:Phenylacetates / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D055672:Static Electricity
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D007211:Indoles; D010648:Phenylacetates; C030374:indole
keywords: DFT; DU145 cell line; Indoles; Perkin–Oglialoro reaction; Prostate cancer; Retinoblastoma protein; VolSurf+; p21(Cip1)