Synthetic Analogue of the Natural Product Piperlongumine as a Potent Inhibitor of Breast Cancer Cell Line Migration

Made available in DSpace on 2018-12-11T17:31:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-03-01. Added 1 bitstream(s) on 2019-10-09T18:32:48Z : No. of bitstreams: 1 S0103-50532017000300475.pdf: 612042 bytes, checksum: 72fdf2c23c51d9f3984b194b81219854 (MD5) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Piperlongumine is a natural amide alkaloid isolated from several species of Piper and is described in the literature as selectively cytotoxic to several cancer cell lines. Inhibiting cell migration has gained considerable interest as an approach for discovering antimetastatic agents because this process is fundamental to metastasis. Piperlongumine, selected from cell-based assay screening of NuBBE Database, inhibited the migration of MDA-MB-231 breast cancer cells with an EC50 of 3.0 � 1.0 μM by the Boyden chamber assay. A series of five analogous compounds based on the structure of piperlongumine were designed, synthesized and evaluated in cell migration and cytotoxicity assays. The analogue designed by molecular simplification ((E)-N-acryloyl-3-(3,4,5-trimethoxyphenyl)acrylamide) was the most active of the series, with an EC50 of 1.5 � 1 μM. Additionally, this compound was selectively cytotoxic, with a selectivity index (SI) of 4.4. N�cleo de Bioensaios Bioss�ntese e Ecofisiologia de Produtos Naturais (NuBBE) Departamento de Qu�mica Org�nica Instituto de Qu�mica Universidade Estadual Paulista (UNESP) Laborat�rio de Qu�mica Medicinal e Computacional Centro de Pesquisa e Inova��o em Biodiversidade e F�rmacos Instituto de F�sica de S�o Carlos Universidade de S�o Paulo (USP) Laborat�rio de Qu�mica Org�nica Sint�tica Instituto de Qu�mica Universidade Estadual de Campinas (UNICAMP) Instituto de Pesquisas de Produtos Naturais (IPPN) Centro de Ci�ncias da Sa�de Universidade Federal do Rio de Janeiro (UFRJ) Laboratoire de Pharmacognosie UMR 8638 COMETE CNRS Facult� de Pharmacie de Paris Universit� Paris Descartes, Sorbonne Paris Cit� N�cleo de Bioensaios Bioss�ntese e Ecofisiologia de Produtos Naturais (NuBBE) Departamento de Qu�mica Org�nica Instituto de Qu�mica Universidade Estadual Paulista (UNESP) FAPESP: 2013/07600-3