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 IC(50) of HPOs was determined using MTT assay. Among these ligands, compound 4e (K(part)=5.02) with an IC(50) of 30 μM and 4f (K(part)=0.1) with an IC(50) of 700 μM showed the lowest and highest IC(50)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.

Keywords: 3-Hydroxypyridin-4-one derivatives; Cytotoxicity; Hela cells; Iron chelators; Partition coefficient.

Fig. 1

Structures of two iron (III) chelators

Fig. 2

Synthesis scheme of 1-substituted-3-hydroxypyridin-4-ones derivatives