Combined dual effect of modulation of human neutrophils' oxidative burst and inhibition of colon cancer cells proliferation by hydroxycinnamic acid derivatives

Bioorg Med Chem. 2016 Aug 15;24(16):3556-64. doi: 10.1016/j.bmc.2016.05.065.

Elisiário J Tavares-da-Silva ¹, Carla L Varela ², Ana S Pires ³, João C Encarnação ⁴, Ana M Abrantes ³, Maria F Botelho ³, Rui A Carvalho ⁵, Carina Proença ⁶, Marisa Freitas ⁶, Eduarda Fernandes ⁶, Fernanda M F Roleira ⁷

Affiliations

1 Pharmaceutical Chemistry Group, Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; CNC.IBILI, University of Coimbra, Portugal. Electronic address: etavares@ff.uc.pt.
2 Pharmaceutical Chemistry Group, Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
3 CNC.IBILI, University of Coimbra, Portugal; Biophysics Institute, IBILI-Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; CIMAGO, FMUC-Faculty of Medicine, University of Coimbra, Portugal.
4 Biophysics Institute, IBILI-Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; CIMAGO, FMUC-Faculty of Medicine, University of Coimbra, Portugal.
5 CNC.IBILI, University of Coimbra, Portugal; Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Portugal.
6 UCIBIO, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
7 Pharmaceutical Chemistry Group, Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; CNC.IBILI, University of Coimbra, Portugal. Electronic address: froleira@ff.uc.pt.

PMID: 27290693 DOI: 10.1016/j.bmc.2016.05.065

Abstract

Colon Cancer is one of the most incident cancers in the Western World. While both genetic and epigenetic factors may contribute to the development of colon Cancer, it is known that chronic inflammation associated to excessive production of reactive oxygen and nitrogen species by phagocytes may ultimately initiate the multistep process of colon Cancer development. Phenolic compounds, which reveal antioxidant and antiproliferative activities in colon Cancer cells, can be a good approach to surpass this problem. In this work, hydroxycinnamic amides and the respective acid precursors were tested in vitro for their capacity to modulate human neutrophils' oxidative burst and simultaneously to inhibit growth of colon Cancer cells. A phenolic amide derivative, caffeic acid hexylamide (CAHA) (4) was found to be the most active compound in both assays, inhibiting human neutrophils' oxidative burst, restraining the inflammatory process, inhibiting growth of colon Cancer cells and triggering mitochondrial dysfunction that leads Cancer cells to Apoptosis. Altogether, these achievements can contribute to the understanding of the relationship between antioxidant and Anticancer activities and based on the structure-activity relationships (SAR) established can be the starting point to find more effective phenolic compounds as Anticancer agents.

Keywords

Antiproliferative; Colon cancer cells; Human neutrophils; Hydroxycinnamic acid derivatives; Oxidative burst; Synthesis.

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