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

Author(s):Show less -

Valli, Marilia ; Altei, Wanessa ; dos Santos, Ricardo N. ; de Lucca, Jr., Emilio C. ; Dessoy, Marco A. ; Pioli, Renan M. ; Cotinguiba, Fernando ; Cachet, Xavier ; Michel, Sylvie ; Furlan, Maysa ; Dias, Luiz C. ; Andricopulo, Adriano D. ; Bolzani, Vanderlan S.

• Document type: Journal article
• Source: Journal of the Brazilian Chemical Society; v. 28, n. 3, SI, p. 475-484, MAR 2017.
• Web of Science Citations: 7

Abstract

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 mu M 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 mu M. Additionally, this compound was selectively cytotoxic, with a selectivity index (SI) of 4.4. (AU)

• FAPESP's process: 10/06741-4 - Structure- and ligand based-drug design of new chemotherapeutic agents for the treatment of cancer
• Grantee: Ricardo Nascimento dos Santos
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 10/17329-7 - NuBBE natural products, micromolecular diversity useful for the rational design of novel anticancer agents
• Grantee: Marilia Valli
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 03/02176-7 - Conservation and sustainable use of the diversity from Cerrado and Atlantic Forest: chemical diversity and prospecting for potential drugs - phase II
• Grantee: Vanderlan da Silva Bolzani
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC