Radical scavenging activity and cytotoxicity of phenethyl ether and cinnamic amide derivatives

Novel phenethyl ether derivatives (PhE) and cinnamic amide derivatives (CA), which have two mono- or polyphenol rings connected either by an ether (PhE) or amide bond (CA), were synthesized. We investigated their ability to scavenge the O2- and DPPH radicals in vitro, using ESR spectroscopy, in relation to their cytotoxic activity against a human oral squamous cell carcinoma (HSC-2) cell line. The radical scavenging activity was considerably influenced by the position of the hydroxyl groups in the benzene rings. Based on their radical scavenging activity and cytotoxicity, these compounds were classified into two groups: active compounds (such as catechol and hydroquinone) and inactive compounds (such as resorcin and phenol). These results suggest a close relationship between the cytotoxic activity and radical scavenging activity derived from ortho-para preference in dihydroxybenzene. PhE and CA might show potential activity in free radical mediated diseases.