Publication Type Journal Article
Title May iron(III) complexes containing phenanthroline derivatives as ligands be prospective anticancer agents?
Authors Cristina P. Matos Zelal Adiguzel Yasemin Yildizhan Buse Cevatemre Tugba Bagci Onder Ozge Cevik Patrique Nunes Liliana P. Ferreira Maria Deus Carvalho Debora L. Campos Fernando R. Pavan J.C. Pessoa Maria Helena Garcia Ana Isabel Tomaz Isabel Correia Ceyda Acilan
Groups BIOIN
Year 2019
Month August
Volume 176
Pages 492-512
Abstract We report the design, synthesis and biological studies on a group of mixed ligand Fe(111) complexes as anti-cancer drug candidates, namely their interaction with DNA, cytotoxicity and mechanism(s) of action. The aim is to obtain stable, efficient and selective Fe-complexes to be used as anti-cancer agents with less damaging side effects than previously reported compounds. Five ternary Fe(III) complexes bearing a tripodal aminophenolate ligand L2-, H2L = N,N-bis(2-hydroxy-3,5-dimethylbenzyl)-N-(2-pyridylmethyl) amine, and different aromatic bases NN = 2,21-bipyridine [Fe(L)(bipy)]PF6 (1), 1,10-phenanthroline [Fe(L)(phen)]PF6 (2), or a phenanthroline derivative co-ligand: [Fe(L)(amphen)]NO3 (3), [Fe(L)(amphen)]PF6 (3a), [Fe(L)(Clphen)]PF6 (4), [Fe(L)(epoxyphen)]PF6 (5) (where amphen = 1,10-phenanthroline5-amine, epoxyphen = 5,6-epoxy-5,6-dihydro-1,10-phenanthroline, Clphen = 5-chloro-1,10-phenanthroline) and the [Fe(L)(EtOH)]NO3 (6) complex are synthesized. The compounds are characterized in the solid state and in solution by elemental analysis, ESI-MS, magnetic susceptibility measurements and FUR, UV-Vis, H-1 and C-13 NMR and fluorescence spectroscopies. [Fe(phen)Cl-3] and [Fe(amphen)Cl-3] were also prepared for comparison purposes. Spectroscopic binding studies indicate groove binding as the main interaction for most complexes with DNA, and for those containing amphen a B- to Z-DNA conformational change is proposed to occur. As determined via M1T analysis all compounds 1-6 are cytotoxic against a panel of three different cell lines (HeLa, H1299, MDA-MB-231). For selected compounds with promising cytotoxic activity, apoptosis was evaluated using cell and DNA morphology, TUNEL, Annexin VPAAD staining and caspase3/7 activity. The compounds induce oxidative DNA damage on plasmid DNA and in cell culture as assessed by 8-oxo-Guanine and gamma H2AX staining. Comet assay confirmed the presence of genomic damage. There is also increased reactive oxygen species formation following drug treatment, which may be the relevant mechanism of action, thus differing from that normally assumed for cisplatin. The Fe(III)-complexes were also tested against strains of M. Tuberculosis (MTb), complex 2 depicting higher anti-MTh activity than several known second line drugs. Hence, these initial studies show prospective anti-cancer and anti-MTb activity granting promise for further studies. (C) 2019 Published by Elsevier Masson SAS.
Book Title
ISSN 0223-5234
EISSN 1768-3254
Conference Name
Bibtex ID ISI:000472686100033
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