Hydroxypyridinone Derivatives: Synthesis And Cytotoxic Evaluation

Hojjat Sadeghi-Aliabadi; Lotfollah Saghaie-Aliabadi; Nariman Tadayonnia; Mina Mirian

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Hydroxypyridinone Derivatives: Synthesis And Cytotoxic Evaluation

Author(s):

Hojjat Sadeghi-Aliabadi¹,

Lotfollah Saghaie-Aliabadi^1,*,

Nariman Tadayonnia²,

Mina Mirian²

1Department of Pharmaceutical Chemistry, School of Pharmacy, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran

2Isfahan Pharmaceutical Research Center, Isfahan University of Medical Sciences, Isfahan, I. R. Iran

Journal of Reports in Pharmaceutical Sciences:Vol. 2, issue 1; 5-15

Published online:Feb 08, 2013

Article type:Research Article

Received:Jan 08, 2013

Accepted:Jan 29, 2013

How to Cite:Hojjat Sadeghi-AliabadiLotfollah Saghaie-AliabadiNariman TadayonniaMina MirianHydroxypyridinone Derivatives: Synthesis And Cytotoxic Evaluation.J Rep Pharm Sci.2(1):e147757.

Abstract

A series of 3-hydroxypyridin-4-one derivatives (HPOs) as bidentate iron (III) chelating agents were synthesized from 3-hydroxypyran-4-ones (maltol and ethyl maltol) in three steps through protection of hydroxyl group. The protected compounds were then reacted with suitable primary amines to give benzylated pyridinones. Finally, the benzyl group was removed by catalytic hydrogenation to produce the desired products. The partition coefficient of the free ligands and their iron (III) complexes were determined in an aqueous/octanol system using shakeflask method. The cytotoxic effects of these iron chelators against MCF-7 and MDA-MB-231 cancer cells were also evaluated using MTT assay. The results revealed that cytotoxicity of synthesized compounds were closely related to the lipophilycity of them so that the most lipophilic compound (4f) showed the highest activity; whereas compound 4a as a more hydrophilic agent showed the lowest cytotoxic effect; Although these compounds were cytotoxic at high concentration (≥ 0.1 mM).

Keywords

3-Hydroxypyridin-4-ones

Iron chelating agents

Lipophilicity

MTT assay

MCF-7 and MDA-MB-231 Cells

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