Synthesis and biological evaluation of bidentate 3-hydroxypyridin-4-ones iron chelating agents

Abstract

A series of 3-hydroxypyridin-4-one derivatives (HPOs) were synthesized and their partition coefficient values (K_part) were determined. The cytotoxic effects of these iron chelators against Hela cancer cells were also evaluated. The IC₅₀ of HPOs was determined using MTT assay. Among these ligands, compound 4e (K_part=5.02) with an IC₅₀ of 30 µM and 4f (K_part=0.1) with an IC₅₀ of 700 µM showed the lowest and highest IC₅₀'s, respectively. In conclusion, the introduction of a more hydrophobic functional group (such as butyl in compound 4e) on the nitrogen of pyridinone ring resulted in higher cytotoxic activity of ligands.