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Effects of Terminal Substitution and Iron Coordination on Antiproliferative Activity of l ‐Proline‐salicylaldehyde–Thiosemicarbazone Hybrids
Author(s) -
Milunović Miljan N. M.,
Dobrova Aliona,
Novitchi Ghenadie,
Gligorijević Nevenka,
Radulović Siniša,
Kožišek Jozef,
Rapta Peter,
Enyedy Eva A.,
Arion Vladimir B.
Publication year - 2017
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.201700962
Subject(s) - chemistry , stereochemistry , hela , semicarbazone , ligand (biochemistry) , medicinal chemistry , in vitro , biochemistry , receptor
A series of five iron(III) complexes, namely [Fe( HL 1 )Cl 2 ] ( 1 ), [Fe( HL 2 )Cl 2 ] · 1.6H 2 O ( 2· 1.6H 2 O), [Fe( HL 3 )(MeOH)Cl 2 ] · 0.5H 2 O ( 3· 0.5H 2 O), [Fe( HL 4 )(MeOH)Cl 2 ] · 0.5H 2 O ( 4· 0.5H 2 O) and [Fe( HL 4 )(DMF)Cl 2 ] · 0.5Et 2 O · H 2 O ( 4′· 0.5Et 2 O · H 2 O), where H 2 L 1 = l ‐proline‐salicylaldehyde–thiosemicarbazone ( l ‐Pro‐STSC), H 2 L 2 = pyrrolidine‐substituted l ‐Pro‐STSC, H 2 L 3 = phenyl‐substituted l ‐Pro‐STSC, and H 2 L 4 = naphthyl‐substituted l ‐Pro‐STSC, have been synthesized. The two ligand precursors ( H 2 L 3 and H 2 L 4 ) and iron complexes were characterized by elemental analysis, spectroscopic methods (UV/Vis, IR, and NMR), ESI mass spectrometry, cyclic voltammetry, and single‐crystal X‐ray crystallography ( 1–3 and 4′ ). Magnetic properties of the five‐coordinate complex 2 and six‐coordinate complex 4 have also been investigated. The antiproliferative activity of the organic hybrids and their iron(III) complexes have been studied in vitro in five human cell lines and one murine cancer cell line, namely HeLa (cervical cancer), FemX (melanoma), A549 (alveolar basal adenocarcinoma), LS‐174 (colon cancer), MDA‐MB‐453 (breast cancer) and MS1 (transformed murine endothelial), as well as in human noncancerous fetal lung fibroblast cell line (MRC‐5). According to the structure–activity relationship, introduction of aromatic groups such as phenyl or naphthyl enhances the cytotoxic potency of the hybrids in the following order H 2 L 1 < H 2 L 2 < H 2 L 3 < H 2 L 4 . Coordination of the hybrids to iron(III) improves their antiproliferative activity in the majority of investigated cell lines with exception of H 2 L 3 in LS‐174, H 2 L 4 in MS1, and both H 2 L 3 and H 2 L 4 in FemX cell lines, where an opposite effect was observed.