Synthesis of Hydroxylated Biphenyl Derivatives Bearing an α,β-Unsaturated Ketone as a Lead Structure for the Development of Drug Candidates against Malignant Melanoma

A small collection of C-2-symmetric hydroxylated biphenyl derivatives featuring an alpha,beta-unsaturated ketone as a lead structure was prepared, and the capacity of these compounds to act as antiproliferative agents against four human malignant melanoma cell lines was assayed. The prodrug approach was applied in order to improve the delivery of compounds into the cell by modulation of the phenolic hydroxy protecting group. The hydroxylated biphenyl structure bearing an alpha,beta-unsaturated ketone and a phenolic-O-prenylated chain was found to facilitate the delivery of the molecule and interactions with biological targets. Four compounds showed antiproliferative activity resulting in IC50 values in the range of 1.2 to 2.8 mu M.

Automated summary

A small collection of C-2-symmetric hydroxylated biphenyl derivatives containing alpha,beta-unsaturated ketone as a lead structure were prepared and assayed for antiproliferative activity against four human malignant melanoma cell lines. The prodrug approach was utilized to enhance delivery of the compounds into cells by modulating the phenolic hydroxy protecting group. The hydroxylated biphenyl structure with alpha,beta-unsaturated ketone and phenolic-O-prenylated chain facilitated molecule delivery and interactions with biological targets, resulting in four compounds showing antiproliferative activity with IC50 values ranging from 1.2 to 2.8 μM.