title: In silico selection and cell-based characterization of selective and bioactive compounds for androgen-dependent prostate cancer cell.
abstract: Prostate cancer is one of the most prevalent types of cancer in male population. It is a hormone driven disease, especially in its initial phase. Hence, androgen deprivation therapy (ADT) is the major chemotherapeutic effort and novel AR inhibitors with improved pharmacological profiles are needed. In this report, a novel bioactive compound was selected and investigated using in silico and cell-based assays. Neq0502 compound was selective for the testosterone stimulated AR-dependent prostate cancer cell (LNCaP, GI50=22.4μM) when compared with unstimulated LNCaP or AR-insensitive (DU145 and PC-3) cell lines. Cell cycle arrest study provided the same profile for Neq0502 and the reference drug enzalutamide. Moreover, this compound is not cytotoxic for fibroblast Balb/C 3T3 clone A31 cells up to 250μM, with a good selectivity ratio (SI>11), which could be used in compound optimization effort to a novel therapeutic alternative.
authors.affiliation: Medicinal Chemistry Group (NEQUIMED), São Carlos Institute of Chemistry (IQSC), University of São Paulo (USP), Av. Trabalhador São-carlense, 400, São Carlos, SP 13566-590, Brazil.
authors.forename: Elisa C Santa
authors.initials: EC
authors.lastname: Cruz
authors.affiliation: Medicinal Chemistry Group (NEQUIMED), São Carlos Institute of Chemistry (IQSC), University of São Paulo (USP), Av. Trabalhador São-carlense, 400, São Carlos, SP 13566-590, Brazil.
authors.forename: Adriel R
authors.initials: AR
authors.lastname: Carecho
authors.affiliation: Medicinal Chemistry Group (NEQUIMED), São Carlos Institute of Chemistry (IQSC), University of São Paulo (USP), Av. Trabalhador São-carlense, 400, São Carlos, SP 13566-590, Brazil.
authors.forename: Marta E
authors.initials: ME
authors.lastname: Saidel
authors.affiliation: Medicinal Chemistry Group (NEQUIMED), São Carlos Institute of Chemistry (IQSC), University of São Paulo (USP), Av. Trabalhador São-carlense, 400, São Carlos, SP 13566-590, Brazil.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Montanari
authors.affiliation: Medicinal Chemistry Group (NEQUIMED), São Carlos Institute of Chemistry (IQSC), University of São Paulo (USP), Av. Trabalhador São-carlense, 400, São Carlos, SP 13566-590, Brazil. Electronic address: andleitao@iqsc.usp.br.
authors.forename: Andrei
authors.initials: A
authors.lastname: Leitão
mesh_terms: D016475:3T3 Cells; D000083:Acetanilides / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000083:Acetanilides; D000970:Antineoplastic Agents; D006575:Heterocyclic Compounds, 3-Ring; C000620855:Neq0502 compound; D011944:Receptors, Androgen
keywords: Androgen ablation; Cell-based screening; Cheminformatics; In vitro assays; Prostate cancer