Cytotoxicity of Benzofuran-Containing Simplified Viniferin Analogues

Abstract

Within the huge class of plant secondary metabolites, resveratrol-derived stilbenoids show wide structural diversity and mediate a great number of biological responses relevant for human health, including cancer prevention and cytotoxicity. Resveratrol is known to modulate several pathways directly linked to cancer progression, as well as its analogue pterostilbene, characterized by an increased metabolic stability and significant pharmacological activities. To study the potential anticancer activity of other stilbenoids, a home-made collection of resveratrol dimers and simplified analogues was tested on melanoma A375, non-small cell lung cancer H460 and PC3 prostate cancer cell lines. The structural determinants responsible for the antiproliferative activity have been highlighted. Moreover, to investigate the DNA damage ability of the selected molecules, the expression of the γ-H2AX after compound exposure was evaluated.

Keywords: DNA damage; antiproliferative activity; benzofuran nucleus; dimeric stilbenoids; viniferin derivatives.

Figure 1

Structures of resveratrol, pterostilbene and dimeric derivatives 3 and 4.

Figure 2

Structure of selected stilbenoid dimers 5–8 and simplified analogues of 7 (9–11, 15, 16) and 8 (12–14, 17). The elicited groups are highlighted in blue (position 2), red (position 3), purple (position 4), green (position 5) and orange (position 6).

Figure 3

Twenty-four hours after seeding, WS1, A375 and H460 cells were exposed to compounds for 48 h at concentrations corresponding to IC₅₀ at 48 h. Cells were then harvested and processed for Western blot assay. Tubulin and actin represent the control for loading; for compounds 1–4, see ref. [8].