In silico selection and cell-based characterization of selective and bioactive compounds for androgen-dependent prostate cancer cell

Autor(es)

Santa Cruz, Elisa C. ; Carecho, Adriel R. ; Saidel, Marta E. ; Montanari, Carlos Alberto ; Leitao, Andrei

• Tipo de documento: Artigo Científico
• Fonte: Bioorganic & Medicinal Chemistry Letters; v. 27, n. 3, p. 546-550, FEB 1 2017.
• Citações Web of Science: 3

Resumo

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, GI(50) = 22.4 mu M) 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 250 mu M, with a good selectivity ratio (SI > 11), which could be used in compound optimization effort to a novel therapeutic alternative. (C) 2016 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 13/18009-4 - Planejamento, síntese e atividade tripanossomicida de inibidores covalentes reversíveis da enzima cruzaína
• Beneficiário: Carlos Alberto Montanari
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/07025-3 - Estudos in silico e ensaios celulares na identificação de novas alternativas terapêuticas para o câncer de próstata
• Beneficiário: Andrei Leitão
• Modalidade de apoio: Auxílio à Pesquisa - Regular