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Synthesis, Modification, and Biological Evaluation of a Library of Novel Water‐Soluble Thiopyridone‐Based Organometallic Complexes and Their Unexpected (Biological) Behavior
Author(s) -
Harringer Sophia,
Happl Barbara,
Ozenil Marius,
Kast Caroline,
Hejl Michaela,
Wernitznig Debora,
Legin Anton A.,
Schweikert Andreas,
Gajic Natalie,
Roller Alexander,
Koellensperger Gunda,
Jakupec Michael A.,
Kandioller Wolfgang,
Keppler Bernhard K.
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201905546
Subject(s) - cytotoxicity , solubility , chemistry , ligand (biochemistry) , aqueous solution , combinatorial chemistry , metal , group 2 organometallic chemistry , polar , organic chemistry , molecule , in vitro , biochemistry , receptor , physics , astronomy
A series of 16 dinuclear thiopyridone‐based organometallics with excellent water solubility, increased stability and remarkable cytotoxicity were synthesized and characterized. The complexes of this work formed dimeric species featuring a double positive charge in polar protic solvents, accounting for their outstanding solubility in aqueous solution. Most of them displayed higher antiproliferative activity than their parental thiomaltol complex, with unexpected cytotoxicity trends depending on the employed metal center, ligand modification, and cell line. Insights into their behavior in biological systems were gathered by means of amino‐acid interaction studies, cytotoxicity tests in 3D spheroid models, laser ablation, cellular accumulation measurements, as well as cell cycle experiments.