Assessment of usable ligand for iron chealating in biological applications

In order to remove excess iron from the body, the synthesis\complexation degree of the ligands that can form a compound with the Fe (III) ion and the efficiency of iron removal from human plasma is the first line of applications that have potential for clinical use in the treatment process. In this study, Initially, 3-methyl-2,4-pentanedione and 3-butyl-2,4-pentanedione which are acetylacetone derivatives with different chain lengths were successfully synthesized by displacement of alkyl groups with active hydrogen on the carbon atom between the two carbonyl compounds present on acetylacetone. Chloralhydrate, Hydroxylamine hydrochloride was used as the starting compound and the anti-monochloroglucoxime and dimethylglyoxime ligands were successfully synthesized. 8-Hydroxyquinoline-5-sulfonic acid, 4,5-Dihydroxybenzene-1,3-disulfonic acid, Pyridine 2,6-Dicarboxylic acid, Nitrilotriacetic acid, Citric acid, Sodium oxalate, Glycine and Salicylic acid were used as the ligand. Iron complexes were synthesized in pure water and plasma. The degree of complexation was determined by ICP-MS and UV-Vis methods. The electrochemical behavior of complexes, ligands was studied by CV. Platinum disk electrot, platinum counter electrode and Ag-AgCl reference electrode were used in the studies. Then the in vitro cytotoxic effect of the complexes synthesized by the cell culture method was determined. MTT assay was used to examine whether the complexes had cytotoxic effect on HUVEC cell line at 5 different concentration ranges (12.5, 25, 50, 100 and 200 μM) and their effect on cell proliferation. Almost all of the complexes used in the study had a negative correlation between the percent cytotoxicity responses at increasing doses. Furthermore, it has been determined that many of the complexes do not have cytotoxic effect on HUVEC and they do not affect cell proliferation or even have therapeutic effect, it appears to be promising for an experimental animal model study during the drug development phase. Investigation of the effect of chelating ligands used in this study has been the first step in the realization of in vivo assays. We anticipate the development of effective iron chelators that will be optimal for iron chelation if the results of this in vitro study are supported by in vivo studies in the future.