Synthesis of NNN Chiral Ruthenium Complexes and Their Cytotoxicity Studies

Abstract

The synthesis and characterization of chiral pincer-ruthenium complexes of the type (R2NNN)­RuCl2 (PPh3) (R = 3-methylbutyl and 3,3-dimethylbutyl) is reported here. The cytotoxicity studies of these complexes were studied and compared with the corresponding activity of achiral complexes. The cytotoxic effect of pincer-ruthenium complexes on human dermal fibroblasts and human tongue carcinoma cells assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay displayed an inhibition of normal and cancer cell growth in a dose-dependent manner. Intracellular reactive oxygen species (ROS) level measurement, lactate dehydrogenase assay, DNA fragmentation, and necrosis studies revealed that treatment with pincer-ruthenium complexes induced a redox imbalance in SAS cells by upregulating ROS generation and caused necrotic cell death by disrupting the cellular membrane integrity.

Ruthenium(II) Diphosphine Complexes with Mercapto Ligands That Inhibit Topoisomerase IB and Suppress Tumor Growth In Vivo

“…Characteristic vibrations assigned to the ν(C− S) and δ(C−S) modes occur in the range 1225−1275 cm −1 (Figures S1−S5). 6,11,14,19 The resolved patterns of resonances in the 1 H and 13 C { 1 H} NMR spectra are consistent with low symmetry of the ruthenium(II) complexes (Figures S6−S31). For all of the ruthenium(II) complexes, the 31 P{ 1 H} NMR spectra presented four distinct signals of double double doublets (ddd), consistent with ABMX pattern spin systems.…”

“…Characteristic vibrations assigned to the ν­(C–S) and δ­(C–S) modes occur in the range 1225–1275 cm –1 (Figures S1–S5). ,,, …”

“…Since the anticancer properties of the first ruthenium complexes were tested, several classes of these metal complexes that exert cytotoxic activity have been investigated both in vitro and in vivo. − The well-established synthetic chemistry of ruthenium provides numerous approaches for the development of new complexes containing this metal, and their structural diversities reflect on their anticancer properties against different types of cancer cells . Cell death induced by ruthenium complexes can occur via different mechanisms of action given that these complexes can inhibit the action of various intracellular and extracellular pharmacological targets that play relevant roles in cellular processes. − …”

Enantioselective Cytotoxicity of Chiral Diphosphine Ruthenium(II) Complexes Against Cancer Cells

“…[11] Notably, the related osmium complexes [OsX(η 6 arene)(NN)] + (X = Cl, I) showed potent anticancer activity and similarities for the pair of enantiomers with IC 50 as low as 0.6 μM. [12,13] Recently, chiral ruthenium complexes with phosphines, [14,15] diiminopyridine ligands [16] and sulfur amino acids, [17] have been reported to display cytotoxic activity against cancer cells.…”

Pd(II)–PPh3 complexes of halogen substituted acylthiourea ligands: Biomolecular interactions and in vitro anti‐proliferative activity

“…[ 51 ] The lipophilic nature of the complexes ( C1–C4 ) due to the presence of PPh 3 also contributes to the enhanced cytotoxicity as seen in literature reports. [ 52 ]…”