Furoxans and tocopherol analogs-furoxan hybrids as anticancer agents.

We determined the antiproliferative and nitric oxide (NO)-releasing activity of furoxans and tocopherol analogs-furoxan hybrids by tandem Griess/resazurin/sulforhodamin B assays in HeLa, 253J, T24, and HepG2 cancer cells. In addition, to investigate the NO implications in the inhibition of cell growth, cells were pretreated with the NO scavenger hemoglobin and the genotoxic damage was determined. The compounds 1 and 3 emerged as good anticancer agents for bladder cancer treatment. The NO-releasing activity of these compounds appears to be necessary to obtain the antiproliferative effect. Although compound 1 exerted a DNA damage mechanism of action, compound 3 seemed to act in a different way. The low toxicity levels against normal cell line HaCaT point them out as a very promising scaffold for the further design of new anticancer agents.