Impact of various lipophilic substituents on ruthenium(II), rhodium(III) and iridium(III) salicylaldimine-based complexes: synthesis, in vitro cytotoxicity studies and DNA interactions

Cassells, Irwin; Stringer, Tameryn; Hutton, Alan T.; Prince, Sharon; Smith, Gregory S.

doi:10.1007/s00775-018-1567-3

Cited by 33 publications

(8 citation statements)

References 40 publications

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“… , The aim of the present study is to investigate the effect of the variation of the metal center between Ru(II) and Pt(II), by keeping the same chloroethylamine motif bearing ligand(s), since Pt(II) complexes containing this particular moiety are scarce − and Ru(II) complexes of the same are not known. However, Pt(II) or Ru(II)- p -cymene complexes of various other salicylaldimine based ligands have shown anticancer activity, stabilization of telomeres, and efficiency in catalysis. − In addition, earlier works show that using one ligand and varying the metal center (Ir, Ru, or Rh) has a substantial impact on the solution stability and also alters the cytotoxicity of a resultant complex against a particular type of cancer. − …”

Section: Introductionmentioning

confidence: 99%

Differences in Stability, Cytotoxicity, and Mechanism of Action of Ru(II) and Pt(II) Complexes of a Bidentate N,O Donor Ligand

et al. 2020

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We report [RuII(L)(η6-p-cym)Cl] (1 and 2) and [PtII(L)(DMSO)Cl] (3 and 4) complexes, where L is a chelate imine ligand derived from chloroethylamine and salicylaldehyde (HL1) or o-vanillin (HL2). The complexes were characterized by single-crystal X-ray diffraction and other analytical techniques. The 1H nuclear magnetic resonance data show that both the Ru(II) and Pt(II) complexes start forming the aquated complex within an hour. The aquated complexes are stable at least up to 24 h. The complexes bind to the N7 of the model nucleobase 9-ethylguanine (9-EtG). Interaction with calf thymus (CT) DNA shows moderate binding interactions with binding constants, K b (3.7 ± 1.2) × 103 M–1 and (4.3 ± 1.9) × 103 M–1 for 1 and 3, respectively. The complexes exhibit significant antiproliferative activity against human pancreas ductal adenocarcinoma (Mia PaCa-2), triple negative metastatic breast adenocarcinoma (MDA-MB-231), hepatocellular carcinoma (Hep G2), and colorectal adenocarcinoma (HT-29) cell lines. The studies show that with the same ligand the Pt(II) complexes are more potent than the Ru(II) complexes. The in vitro potencies of all the complexes toward pancreatic cancer cell line MIA PaCa-2 are more than cisplatin (CDDP). The Pt(II) and Ru(II) complexes show similar binding constants with CT-DNA, but the reactivity of the Pt(II) complex 3 with 9-EtG is faster and their overall cell killing pathways are different. This is evident from the arrest of the cell cycle by the Ru(II) complex 1 in the G2/M phase in contrast to the SubG1 phase arrest by the Pt(II) complex 3. The immunoblot study shows that 3 increases cyclin D and Bcl-2 expression in MDA-MB-231 due to the SubG1 phase arrest where these proteins express in greater quantities. However, both 1 and 3 kill in the apoptotic pathway via dose-dependent activation of caspase 3. Complex 3 depolarizes the mitochondria more efficiently than 1, suggesting its higher preference for the intrinsic pathway of apoptosis. Our work reveals that the same bidentate ligand with a change of the metal center, viz, Pt(II) or Ru(II), imparts significant variation in cytotoxic dosage and pathway of action due to specific intrinsic properties of a metal center (viz, coordination geometry, solution stability) manifested in a complex.

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Section: Introductionmentioning

confidence: 99%

Differences in Stability, Cytotoxicity, and Mechanism of Action of Ru(II) and Pt(II) Complexes of a Bidentate N,O Donor Ligand

et al. 2020

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“…Selection of the complexes was mainly governed by their well-characterized and somewhat different solution chemical properties and not by the otherwise poor cytotoxic efficacy of the complexes. These selected complexes, however, are good models of in vitro active compounds, e.g., (O,O) donor flavone and naphtoquinone-type complexes of Ru(η 6 - p -cym) or (O,N) donor 8-hydroxyquinoline or Schiff-base complexes of both metal ions [72, 80–85]. It was shown previously that interaction of the studied complexes with HSA is possible, both by loss of the bidentate ligand or by the loss of only chlorido leaving group [49].…”

Section: Resultsmentioning

confidence: 99%

Binding mechanisms of half-sandwich Rh(III) and Ru(II) arene complexes on human serum albumin: a comparative study

Dömötör

Enyedy

2019

J Biol Inorg Chem

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Various half-sandwich ruthenium(II) arene complexes and rhodium(III) arene complexes have been intensively investigated due to their prominent anticancer activity. The interaction of the organometallic complexes of Ru(η 6 - p -cymene) and Rh(η 5 -C 5 Me 5 ) with human serum albumin (HSA) was studied in detail by a combination of various methods such as ultrafiltration, capillary electrophoresis, 1 H NMR spectroscopy, fluorometry and UV–visible spectrophotometry in the presence of 100 mM chloride ions. Binding characteristics of the organometallic ions and their complexes with deferiprone, 2-picolinic acid, maltol, 6-methyl-2-picolinic acid and 2-quinaldic acid were evaluated. Kinetic aspects and reversibility of the albumin binding are also discussed. The effect of low-molecular-mass blood components on the protein binding was studied in addition to the interaction of organorhodium complexes with cell culture medium components. The organometallic ions were found to bind to HSA to a high extent via a coordination bond. Release of the bound metal ions was kinetically hindered and could not be induced by the denaturation of the protein. Binding of the Ru(η 6 - p -cymene) triaqua cation was much slower (ca. 24 h) compared to the rhodium congener (few min), while their complexes interacted with the protein relatively fast (1–2 h). The studied complexes were bound to HSA coordinatively. The highly stable and kinetically inert 2-picolinate Ru(η 6 - p -cymene) complex bound in an associative manner preserving its original entity, while lower stability complexes decomposed partly or completely upon binding to HSA. Fast, non-specific and high-affinity binding of the complexes on HSA highlights their coordinative interaction with various types of proteins possibly decreasing effective drug concentration. Graphic abstract Electronic supplementary material The online version of this article (10.1007/s00775-019-01683-0) contains supplementary material, which is available to authorized users.

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“…The ability of the drugs to induce either apoptosis or necrosis seems to be a primary factor in determining their anti‐cancer efficacy . The cytotoxicity of the three complexes and their ligands were determined in terms of a colorimetric microculture assay (MTT) in HeLa and KB cells, yielding IC 50 values shown in Table , which also shows the comparison of experimental conditions with the results of cisplatin experiments.…”

Section: Resultsmentioning

confidence: 99%

Structure and cytotoxicity of zinc (II) and cobalt (II) complexes based on 1,3,5‐tris(1‐imidazolyl) benzene

Zhu

Zhao

Peng

et al. 2019

Applied Organom Chemis

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Three novel complexes, [Zn (tib)2·(H2O)2]·(NO3)2 (1), [Co (tib)2]·2NO3 (2) and [Co2(tib)2(btc)]·H2O (3) [H4btc = 1,2,4,5‐benzenetetracarboxylic acid; H2tib = 1,3,5‐tris(1‐imidazolyl)benzene], were synthesized and characterized by single‐crystal X‐ray, IR and elemental analysis. The interaction of these complexes with FS‐DNA (fish sperm DNA) was monitored, and binding constants were determined using UV/Vis, which revealed that they have the ability to bind to FS‐DNA. DNA‐binding constants (K) for the three complexes were 2.2 × 104 m−1, 0.7 × 104 m−1 and 0.09 × 104 m−1, respectively. The interaction capacity of the complexes with FS‐DNA has been investigated by fluorescence spectroscopy. Stern–Volmer quenching plot values for complexes 1, 2 and 3 were 0.3784, 0.1028 and 0.076, respectively. The viscosity measurement suggested that complexes 1, 2 and 3 interact with DNA in an intercalation mode. In addition, anti‐cancer activities of these complexes investigated through MTT assays in vitro indicated that the complexes showed good cytotoxic activity against cancer cell lines. Cytotoxic activity of test complexes against two different cancer cell lines (HeLa and KB cells) showed significant cancer cell inhibition rates. Flow cytometry experiments and morphological apoptosis studies showed that the complexes induced apoptosis of HeLa tumor cell lines. Finally, a further molecular docking technique was employed to confirm the binding of the complexes toward the molecular target DNA.

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Impact of various lipophilic substituents on ruthenium(II), rhodium(III) and iridium(III) salicylaldimine-based complexes: synthesis, in vitro cytotoxicity studies and DNA interactions

Cited by 33 publications

References 40 publications

Differences in Stability, Cytotoxicity, and Mechanism of Action of Ru(II) and Pt(II) Complexes of a Bidentate N,O Donor Ligand

Differences in Stability, Cytotoxicity, and Mechanism of Action of Ru(II) and Pt(II) Complexes of a Bidentate N,O Donor Ligand

Binding mechanisms of half-sandwich Rh(III) and Ru(II) arene complexes on human serum albumin: a comparative study

Structure and cytotoxicity of zinc (II) and cobalt (II) complexes based on 1,3,5‐tris(1‐imidazolyl) benzene

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