A hypoxia efficient imidazole-based Ru(ii) arene anticancer agent resistant to deactivation by glutathione

Abstract

A slow hydrolyzing imidazole-based Ru(II)-arene complex [(L)Ru(II)(η(6)-p-cym)(Cl)](PF6) (1) with excellent stability in the extracellular chloride concentration shows better activity under hypoxia and strong resistance to glutathione (GSH) in vitro under hypoxic conditions. 1 arrests the cell cycle in sub G1 and G2/M phases and leads to apoptosis.

Biological and catalytic evaluation of Ru(II)‐p‐cymene complexes of Schiff base ligands: Impact of ligand appended moiety on photo‐induced DNA and protein cleavage, cytotoxicity and C‐H activation

“…The asymmetric unit of 1 and 2 contains a cationic complex and lattice PF 6 anion. The Ru(II) metal center of complex 1 and 2 is coordinated with all the six carbon atoms of p ‐cymene ring, both the nitrogen atoms (N1, N2) of bidentate ligand and chlorido ligand (Cl1) in a pseudo‐octahedral fashion . The N1 and N2 nitrogen atoms of bidentate ligand and chlorido ligand constitute the three legs of the ‘piano‐stool’ structure of the complexes.…”

Alteration of steric hindrance modulates glutathione resistance and cytotoxicity of three structurally related RuII-p-cymene complexes

“…41 C1 also exhibits better activity in hypoxia although the activity is decreased in the presence of excess GSH in hypoxia. 41 Cell cycle analysis. The effect of complexes (1, 2) on the cell cycle of MCF-7 was probed with two different concentrations (4 and 6 μM) of each complex and the observation shows that the percentage of cell population in the S and G2/M phases are comparatively higher with respect to the control (Table 3, ESI, Fig.…”

“…The Schiff base ligands (L1-L2) were synthesized using a similar procedure as described by us earlier. 41 The reaction of one mole equivalent of [Ru II 2 (η 6 -p-cym) 2 Cl 4 ] precursor with ca. 2.4 mole equivalents of the respective ligand in methanolic solution led to the formation of respective complexes (Scheme 1).…”

“…S28 and S29 †), whereas for 3, we found an increase in the sub G1 population along with the G2/M phase arrest. 41 DNA ladder assay. Genomic DNA fragmentation, known as the hallmark of apoptosis, 43 was observed in the ladder assay for all of the three complexes.…”

“…We recently have shown that complex 3 shows in vitro cytotoxicity in certain cancer cell lines and there is little deactivation in the presence of glutathione under hypoxic conditions. 41 In addition no GSH binding was observed by NMR studies. We have synthesized two more isostructural complexes where the only difference lies in the substitution at the vicinity of the metal centre so as to correlate with the effect of steric hindrance on the hydrolysis, anticancer activity, glutathione binding and the pathways of cytotoxicity which is strongly related to the breaking and making of new bonds with the metal centre leading to the pattern of reactivity.…”