Study of Anti‐Apoptotic mechanism of Ruthenium (II)Polypyridyl Complexes via RT‐PCR and DNA binding

Vuradi, Ravi Kumar; Nambigari, Navaneetha; Pushpanjali, Pendyala; Gopu, Srinivas; Kotha, Laxma Reddy; Deepika, G; M., Vinoda Rani; Satyanarayana, S.

doi:10.1002/aoc.5332

Cited by 10 publications

(5 citation statements)

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“…Ruthenium is one of the most investigated non-Pt metals for cancer treatment: Ru(III) complexes, especially NAMI-type ones, are useful for their excellent antimetastatic properties [26]. Moreover, polypyridyl Ru(II) complexes have been extensively investigated as a possible DNA "light switch", with interesting photophysical and cell migration inhibition properties [27]. Another promising strategy to improve the anticancer efficacy of platinum drugs and overcome their shortcomings is incorporating a second metal center with distinct biological targets, oxidation states, and ligand(s) of different natures into platinum complexes, which could influence their modes of action [28].…”

Section: Introductionmentioning

confidence: 99%

The Challenging Treatment of Cisplatin-Resistant Tumors: State of the Art and Future Perspectives

et al. 2023

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One of the main problems in chemotherapy using platinum drugs as anticancer agents is the resistance phenomenon. Synthesizing and evaluating valid alternative compounds is challenging. This review focuses on the last two years of progress in the studies of platinum (II)- and platinum (IV)-based anticancer complexes. In particular, the research studies reported herein focus on the capability of some platinum-based anticancer agents to bypass resistance to chemotherapy, which is typical of well-known drugs such as cisplatin. Regarding platinum (II) complexes, this review deals with complexes in trans conformation; complexes containing bioactive ligands, as well as those that are differently charged, all experience a different reaction mechanism compared with cisplatin. Regarding platinum (IV) compounds, the focus was on complexes with biologically active ancillary ligands that exert a synergistic effect with platinum (II)-active complexes upon reduction, or those for which controllable activation can be realized thanks to intracellular stimuli.

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Section: Introductionmentioning

confidence: 99%

The Challenging Treatment of Cisplatin-Resistant Tumors: State of the Art and Future Perspectives

et al. 2023

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“…In particular, ruthenium-type compounds have been investigated against various cancer cell lines as prospective substitutes for the well-known diamine-dichloroplatinum (II) in the formulation of novel anticancer medicines (cisplatin) [ 22 ]. Under physiological circumstances, ruthenium can access the +2 and +3 oxidation states and can bind to cells’ proteins, nucleic acids, sulfur, or oxygen-containing molecules [ 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Additionally, depending on the characteristics of their ligand, ruthenium complexes can optimize the kinetics of their interactions with cell components.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Ruthenium(II) N-Heterocyclic Carbene Complexes as Enzymatic Inhibitory Agents with Antioxidant, Antimicrobial, Antiparasitical and Antiproliferative Activity

et al. 2023

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A series of [RuCl2(p-cymene)(NHC)] complexes were obtained by reacting [RuCl2(p-cymene)]2 with in situ generated Ag-N-heterocyclic carbene (NHC) complexes. The structure of the obtained complexes was determined by the appropriate spectroscopy and elemental analysis. In addition, we evaluated the biological activities of these compounds as antienzymatic, antioxidant, antibacterial, anticancer, and antiparasitic agents. The results revealed that complexes 3b and 3d were the most potent inhibitors against AchE with IC50 values of 2.52 and 5.06 μM mL−1. Additionally, 3d proved very good antimicrobial activity against all examined microorganisms with IZ (inhibition zone) over 25 mm and MIC (minimum inhibitory concentration) < 4 µM. Additionally, the ligand 2a and its corresponding ruthenium (II) complex 3a had good cytotoxic activity against both cancer cells HCT-116 and HepG-2, with IC50 values of (7.76 and 11.76) and (4.12 and 9.21) μM mL−1, respectively. Evaluation of the antiparasitic activity of these complexes against Leishmania major promastigotes and Toxoplasma gondii showed that ruthenium complexes were more potent than the free ligand, with an IC50 values less than 1.5 μM mL−1. However, 3d was found the best one with SI (selectivity index) values greater than 5 so it seems to be the best candidate for antileishmanial drug discovery program, and much future research are recommended for mode of action and in vivo evaluation. In general, Ru-NHC complexes are the most effective against L. major promastigotes.

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“…Unlike covalent DNA binders (e.g., Cis‐Pt), noncovalent agents engage the phosphate backbone and/or the nucleotides heterocycles through hydrogen bonding, π stacking, electrostatic, or van der Waals interactions. [ 39 ] These molecules are reversible binders and anchor between the base pairs or in the DNA grooves.…”

Section: Resultsmentioning

confidence: 99%

New heteroleptic lanthanide complexes as multimodal drugs: Cytotoxicity studies, apoptosis, cell cycle analysis, DNA interactions, and protein binding

Arbănași

Musat

Mihăilă³

et al. 2020

Applied Organom Chemis

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We report herein the synthesis and characterization of four new heteroleptic complexes of Sm(III), Eu(III), Gd(III), and Tb(III) with the natural flavonoid 5-hydroxyflavone (primuletin) and 1,10-phenanthroline. According to the physicochemical characterization, the mononuclear complexes correspond to the general formula [Ln(OH) 2 L 1 L 2 ]ÁnH 2 O, where L 1 = C 15 H 9 O 3 (deprotonated 5-hydroxyflavone) and L 2 = C 12 H 8 N 2 (1,10-phenanthroline), Ln is the lanthanide cation, and n = 4 for Sm(III), 3.5 for Eu(III), 2 for Gd(III), and 3 for Tb(III). A six-coordinated distorted octahedron geometry was proposed for the complexes, and density functional theory (DFT) studies were used to calculate their optimized geometry. Cytotoxicity was studied using MTS assay on cervical, colorectal, colon, breast, and ovarian adenocarcinoma cell lines. Flow cytometry data were consistent with apoptotic cell death and disruption of the cell cycle in cervical and colon cancer cells. As a means to investigate the mechanism underlying the cytotoxic effects, the abilities of the complexes to interact with calf thymus DNA, human serum albumin, and transferrin have also been assessed. According to experimental and computational studies, the four lanthanide complexes act as DNA intercalators and bind strongly to serum proteins.

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Study of Anti‐Apoptotic mechanism of Ruthenium (II)Polypyridyl Complexes via RT‐PCR and DNA binding

Cited by 10 publications

References 58 publications

The Challenging Treatment of Cisplatin-Resistant Tumors: State of the Art and Future Perspectives

The Challenging Treatment of Cisplatin-Resistant Tumors: State of the Art and Future Perspectives

Evaluation of Ruthenium(II) N-Heterocyclic Carbene Complexes as Enzymatic Inhibitory Agents with Antioxidant, Antimicrobial, Antiparasitical and Antiproliferative Activity

New heteroleptic lanthanide complexes as multimodal drugs: Cytotoxicity studies, apoptosis, cell cycle analysis, DNA interactions, and protein binding

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