4-Substituted-2-Methoxyphenol: Suitable Building Block to Prepare New Bioactive Natural-like Hydroxylated Biphenyls

A small collection of eugenol- and curcumin-analog hydroxylated biphenyls was prepared by straightforward methods starting from natural 4-substituted-2-methoxyphenols and their antitumoral activity was evaluated in vitro. Two curcumin-biphenyl derivatives showed interesting growth inhibitory activities on different malignant melanoma cell lines with IC50 ranging from 13 to 1 mM. Preliminary molecular modeling studies were carried out to evaluate conformations and dihedral angles suitable for antiproliferative activity in hydroxylated biphenyls bearing a side aliphatic chain.