Synthesis and in vitro biological evaluation of nitric oxide-releasing derivatives of hydroxylcinnamic acids as anti-tumor agents

Novel furoxan-based nitric oxide-releasing derivatives 6a-p of hydroxylcinnamic acids were synthesized by coupling the carboxyl group of hydroxylcinnamic acids with furoxan through various alkylol amines. Compounds 6a, e-i and m-p displayed more potent anti-tumor activities superior to control 5-fluorouracil (5-FU) in most cancer cells tested. Furthermore, 6f could selectively inhibit tumor cells, but not non-tumor cell proliferation. This inhibition was attributed to high levels of NO released in cancer cells and potentially synergistic effect of NO donor moieties and the bioactivity of hydroxylcinnamic acids.