Effect of an Imidazole-Containing Schiff Base of an Aromatic Sulfonamide on the Cytotoxic Efficacy of N,N-Coordinated Half-Sandwich Ruthenium(II) <i>p</i>-Cymene Complexes

Maji, Moumita; Acharya, Sourav; Bhattacharya, Indira; Gupta, Arnab; Mukherjee, A.

doi:10.1021/acs.inorgchem.0c03706

Cited by 33 publications

(27 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The iodido-coordinated complexes ( 2 , 4 , 6 , and 8 ) display higher lipophilicity values than their chlorido analogues ( 1 , 3 , 5 , and 7 ). The enhancement in the lipophilicity due to the incorporation of iodido coordination correlates well with our earlier results. , Similarly, introducing the halide into the ligand and increasing its size while keeping the chlorido coordination the same shows an increase in the lipophilicity from complexes L1 to L4 ( 1 < 3 < 5 < 7 ). The presence of 4-iodopyrazole in L4 makes the respective metal complex 7 much more lipophilic than the iodido-coordinated 2 .…”

Section: Resultsmentioning

confidence: 99%

Cytotoxic Ruthenium(II) Complexes of Pyrazolylbenzimidazole Ligands That Inhibit VEGFR2 Phosphorylation

Chakraborty¹,

Roy²,

Chakraborty³

et al. 2021

Inorg. Chem.

Self Cite

View full text Add to dashboard Cite

Eight new ruthenium(II) complexes of N,N-chelating pyrazolylbenzimidazole ligands of the general formula [Ru II (p-cym)(L)-X] + [where the ligand L is 2-(1H-pyrazol-1-yl)-1H-benzo [d]imidazole (L1) substituted at the 4 position of the pyrazole ring by Cl (L2), Br (L3), or I (L4) and X = Cl − and I − ] were synthesized and characterized using various analytical techniques. Complexes 1 and 3 were also characterized by single-crystal X-ray crystallography, and they crystallized as a monoclinic crystal system in space groups P2 1 /n and P2 1 /c, respectively. The complexes display good solution stability at physiological pH 7.4. The iodido-coordinated pyrazolylbenzimidazole ruthenium(II) p-cymene complexes (2, 4, 6, and 8) are more resistant toward hydrolysis and have less tendency to form monoaquated complexes in comparison to their chlorido analogues (1, 3, 5, and 7). The halido-substituted 2-(1H-pyrazol-1-yl)-1H-benzo[d]imidazole ligands, designed as organic-directing molecules, inhibit vascular endothelial growth factor receptor 2 (VEGFR2) phosphorylation. In addition, the ruthenium(II) complexes display a potential to bind to DNA bases. The cytotoxicity profile of the complexes (IC 50 ca. 9−12 μM for 4−8) against the triple-negative breast cancer cells (MDA-MB-231) show that most of the complexes are efficient. The lipophilicity and cellular accumulation data of the complexes show a good correlation with the cytotoxicity profile of 1−8. The representative complexes 3 and 7 demonstrate the capability of arresting the cell cycle in the G2/M phase and induce apoptosis. The inhibition of VEGFR2 phosphorylation with the representative ligands L2 and L4 and the corresponding metal complexes 3 and 7 in vitro shows that the organic-directing ligands and their complexes inhibit VEGFR2 phosphorylation. Besides, L2, L4, 3, and 7 inhibit the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and proto-oncogene tyrosine-protein kinase (Src), capable of acting downstream of VEGFR2 as well as independently. Compounds L2, L4, 3, and 7 have a lesser effect on ERK1/2 and more prominently affect Src phosphorylation. We extended the study for L2 and 3 in the Tg(fli1:gfp) zebrafish model and found that L2 is more effective in vivo compared to 3 in inhibiting angiogenesis.

show abstract

Section: Resultsmentioning

confidence: 99%

Cytotoxic Ruthenium(II) Complexes of Pyrazolylbenzimidazole Ligands That Inhibit VEGFR2 Phosphorylation

Chakraborty¹,

Roy²,

Chakraborty³

et al. 2021

Inorg. Chem.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Pt drugs have achieved great success in the field of cancer chemotherapy. − However, the side effect of these Pt drugs has led chemotherapy research toward alternate anticancer agents such as Ru, Rh, Ir, and Os complexes. − In particular, organometallic half-sandwich complexes of some platinum group metals (Ru, Rh, Ir, and Os) have received considerable attention due to their easy tunable structure, high potency toward cancer cells, and specific mechanism of actions (MoAs). − Generally, the central metals of these 18-electron complexes [(η 5 -Cp)/(η 6 -arene)M(XY)Cl] 0/+ (Cp = functionalized cyclopentadienyl; M = Ru, Rh, Ir, Os; XY = bidentate ligands) have adopted six-coordinated geometry, where the chlorine atom, the bidentate ligand XY, and η 5 -Cp/η 6 -arene occupy one coordination site, two coordination sites, and three coordination sites, respectively (Scheme , I ). It should be noted that hydrolysis of M–Cl bonds, i.e., Cl – /H 2 O exchange, usually represents an activation step for these 18-electron complexes, since M–H 2 O aqua were usually more reactive than the corresponding chloride analogues .…”

Section: Introductionmentioning

confidence: 99%

16-Electron Half-Sandwich Rhodium(III), Iridium(III), and Ruthenium(II) Complexes as Lysosome-Targeted Anticancer Agents

Gao

Guo

et al. 2021

Organometallics

View full text Add to dashboard Cite

The 18-electron half-sandwich platinum group (Rh, Ru, Ir, and Os) metal anticancer complexes have been largely reported due to their easy tunable structure, high potency toward cancer cells, and specific mechanism of actions. However, the 16electron (without the leaving group Cl − ) half-sandwich complexes and their biological evaluation are rarely investigated. With an easy access to the required α-keto-β-diimine ligands using m-CPBA as oxidant, we herein reported the synthesis and characterization of a panel of structurally related 16-electron piano-stool rhodium, iridium, and ruthenium complexes through the rearranged coordination reaction. These complexes have been well-established by NMR spectroscopy, mass spectrometry, single-crystal X-ray crystallography, and elemental analysis. Each of these complexes was stable and exhibited fluorescence in solution. Although no reaction with nucleobase (9-EtG and 9-MeA) was observed, the representative Rh5 showed affinity toward CT-DNA. These 16electron complexes showed promising activity toward A549 and HeLa cancer cells with the values of IC 50 in the range 7.1−32.3 μM, which was comparable to or even better than cisplatin. In addition, the structure−activity relationships were observed that the change of the metal center from iridium(III) and ruthenium(II) to rhodium(III) could enhance the cytotoxicity of these unsaturated complexes. The investigation of mechanism of actions (MoAs) using flow cytometry displayed that the cytotoxicity of the complex Rh5 was associated with the perturbation of the cell cycle and the induction of cell apoptosis. Moreover, microscopic analysis by confocal microscopy suggested that the representative 16-electron complex Rh5 entered A549 cells via energy-dependent pathway and predominantly accumulated in lysosomes, thus resulting in the disruption of lysosomal integrity.

show abstract

“…The complexes productively tied with 9‐EtG and had more slow reactivity toward thiol. Consequently, the sulphonamide and imidazole‐based ruthenium (II) p‐cymene complexes gave an attractive strategy to impart selectivity [136] …”

Section: Resultsmentioning

confidence: 99%

“…Consequently, the sulphonamide and imidazole-based ruthenium (II) p-cymene complexes gave an attractive strategy to impart selectivity. [136] Liu et al ( 2015) prepared novel N-substituted carbazole imidazolium salt derivatives (75; 75 a-75 g) and investigated their cytotoxic activity by MTS assay (Figure 33). Selected human tumor cell lines were HL-60 (myeloid leukemia), SMMC-7721 (liver cancer), A549 (lung cancer), MCF-7 (breast cancer) and SW480 (colon cancer).…”

Section: Chemistryselectmentioning

confidence: 99%

An Insight into the Biological Properties of Imidazole‐Based Schiff Bases: A Review

2021

View full text Add to dashboard Cite

Imidazole is an azole heterocycle containing two non-adjacent nitrogen atoms added greatly to natural products and synthetic compounds. The planar ring system associated with electronrich nitrogen donors are essential for the greater affinity of imidazole derivatives to bind with various bio receptors and enzymes via weak interactions. It improves the pharmacokinetic properties of the pilot molecules consequently utilized as a solution for aqueous solubility, bioavailability, and toxicity parameters since it is a polar compound. An organic molecule with imidazole derivatives has acquired a sustainable place in medical and clinical fields. The consolidation of the imidazole unit is a significant synthetic technique in drug development.The imidazole-based Schiff bases with enormous therapeutic properties has encouraged the scientists to focus on recently initiated novel chemotherapeutic agents such as anticancer, antimicrobial, antioxidant, antiviral, antileishmanial, etc. Imidazole drugs have expanded the degree of curing different dispositions in clinical medications. Herein, we have reported the structural feature of imidazole, design, synthesis of imidazole derivatives, and its significance. This review aims to describe the reported materials of imidazole-based Schiff bases and their derivatives which offer fruitful scope in the field of medicinal chemistry.

show abstract

Effect of an Imidazole-Containing Schiff Base of an Aromatic Sulfonamide on the Cytotoxic Efficacy of N,N-Coordinated Half-Sandwich Ruthenium(II) p-Cymene Complexes

Cited by 33 publications

References 64 publications

Cytotoxic Ruthenium(II) Complexes of Pyrazolylbenzimidazole Ligands That Inhibit VEGFR2 Phosphorylation

Cytotoxic Ruthenium(II) Complexes of Pyrazolylbenzimidazole Ligands That Inhibit VEGFR2 Phosphorylation

16-Electron Half-Sandwich Rhodium(III), Iridium(III), and Ruthenium(II) Complexes as Lysosome-Targeted Anticancer Agents

An Insight into the Biological Properties of Imidazole‐Based Schiff Bases: A Review

Contact Info

Product

Resources

About