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Tunable Anticancer Activity of Furoylthiourea‐Based Ru II –Arene Complexes and Their Mechanism of Action
Author(s) -
Swaminathan Srividya,
Haribabu Jebiti,
Kalagatur Naveen Kumar,
Nikhil Maroli,
Balakrishnan Nithya,
Bhuvanesh Nattamai S. P.,
Kadirvelu Krishna,
Kolandaivel Ponmalai,
Karvembu Ramasamy
Publication year - 2021
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.202004954
Subject(s) - substituent , chemistry , benzene , stereochemistry , ruthenium , ligand (biochemistry) , apoptosis , glutathione , medicinal chemistry , receptor , biochemistry , catalysis , enzyme , organic chemistry
Fourteen new Ru II –arene ( p ‐cymene/benzene) complexes ( C1 – C14 ) have been synthesized by varying the N ‐terminal substituent in the furoylthiourea ligand and satisfactorily characterized by using analytical and spectroscopic techniques. Electrostatic potential maps predicted that the electronic effect of the substituents was mostly localized, with some influence seen on the labile chloride ligands. The structure–activity relationships of the Ru– p ‐cymene and Ru–benzene complexes showed opposite trends. All the complexes were found to be highly toxic towards IMR‐32 cancer cells, with C5 (Ru– p ‐cymene complex containing C 6 H 2 (CH 3 ) 3 as N ‐terminal substituent) and C13 (Ru–benzene complex containing C 6 H 4 (CF 3 ) as N ‐terminal substituent) showing the highest activity among each set of complexes, and hence they were chosen for further study. These complexes showed different behavior in aqueous solutions, and were also found to catalytically oxidize glutathione. They also promoted cell death by apoptosis and cell cycle arrest. Furthermore, the complexes showed good binding ability with the receptors Pim‐1 kinase and vascular endothelial growth factor receptor 2, commonly overexpressed in cancer cells.