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Substitution‐Modulated Anticancer Activity of Half‐Sandwich Ruthenium(II) Complexes with Heterocyclic Ancillary Ligands
Author(s) -
Mitra Raja,
Samuelson Ashoka G.
Publication year - 2014
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.201402205
Subject(s) - chemistry , ruthenium , ligand (biochemistry) , hydrogen bond , halogen , intramolecular force , stereochemistry , thioredoxin reductase , medicinal chemistry , combinatorial chemistry , molecule , alkyl , enzyme , organic chemistry , catalysis , receptor , thioredoxin , biochemistry
Ten new organometallic half‐sandwich ruthenium complexes with heterocyclic ligands have been synthesized ( H1 – H10 ). The substituents on the ancillary heterocyclic ligands were varied to understand the effect of substitution on anticancer activity. The crystallographic characterization of five complexes confirms that they adopt “three‐legged piano‐stool” structures and are stabilized by intramolecular hydrogen bonding. Complexes H2 and H3 also exhibit halogen bonding in the solid state. In aqueous media, the complexes form dinuclear ruthenium species. Complex H1 with a noncytotoxic heterocycle, 6‐fluoro‐2‐mercaptobenzothiazole, and complex H11 with the unsubstituted 2‐mercaptobenzothiazole are the most active against A2780 and KB cell lines. The substitution of the H atoms on the ancillary ligand with Cl or Br atoms leads to a decrease in the anticancer activity. With the exception of fluorine‐substituted H5 , the complexes with mercaptobenzoxazole ( H6 – H9 ) are inactive against all of the tested cell lines. Ruthenium complexes with mercaptonaphthimidazole ( H10 ) and mercaptobenzimidazole ( H13 ) do not show any anticancer activity. The active complexes show a biphasic melting curve when incubated with calf thymus (CT) DNA. These complexes only inhibit thioredoxin reductase (TrxR) enzyme activity to a small extent. The substitution of hydrogen atoms with fluorine atoms in the aromatic heterocyclic ligands on organometallic half‐sandwich ruthenium complexes has the most beneficial effect on their anticancer activity.