Recent development of transition metal complexes with in vivo antitumor activity

Liang, Jiaxin; Zhong, Hai‐Jing; Yang, Guan–Jun; Vellaisamy, Kasipandi; Ma, Dik‐Lung; Leung, Chung‐Hang

doi:10.1016/j.jinorgbio.2017.06.002

Cited by 89 publications

(53 citation statements)

References 65 publications

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“…Afterwards, novel anticancer agents based on metals different from platinum were developed, as extensively reported in several review articles [16][17][18][19][20][21][22][23]. Among all the metal derivatives thus far investigated, ruthenium complexes in the +2 and +3 oxidation states gained increasing attention as valuable alternatives to Pt(II)-based ones [24][25][26][27][28][29][30][31][32][33].…”

Section: From Platinum(ii) To Ruthenium(iii)-based Complexes: the Impmentioning

confidence: 99%

Anticancer Ruthenium(III) Complexes and Ru(III)-Containing Nanoformulations: An Update on the Mechanism of Action and Biological Activity

et al. 2019

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The great advances in the studies on metal complexes for the treatment of different cancer forms, starting from the pioneering works on platinum derivatives, have fostered an increasingly growing interest in their properties and biomedical applications. Among the various metal-containing drugs investigated thus far, ruthenium(III) complexes have emerged for their selective cytotoxic activity in vitro and promising anticancer properties in vivo, also leading to a few candidates in advanced clinical trials. Aiming at addressing the solubility, stability and cellular uptake issues of low molecular weight Ru(III)-based compounds, some research groups have proposed the development of suitable drug delivery systems (e.g., taking advantage of nanoparticles, liposomes, etc.) able to enhance their activity compared to the naked drugs. This review highlights the unique role of Ru(III) complexes in the current panorama of anticancer agents, with particular emphasis on Ru-containing nanoformulations based on the incorporation of the Ru(III) complexes into suitable nanocarriers in order to enhance their bioavailability and pharmacokinetic properties. Preclinical evaluation of these nanoaggregates is discussed with a special focus on the investigation of their mechanism of action at a molecular level, highlighting their pharmacological potential in tumour disease models and value for biomedical applications.

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Section: From Platinum(ii) To Ruthenium(iii)-based Complexes: the Impmentioning

confidence: 99%

Anticancer Ruthenium(III) Complexes and Ru(III)-Containing Nanoformulations: An Update on the Mechanism of Action and Biological Activity

et al. 2019

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“…3 Recently, a great number of ruthenium complexes containing different ligands, have been tested as antitumor agents against different kinds of tumor cell lines, showing to be very active. [4][5][6][7][8][9] Thus, picolinate containing complex [Ru(η 6 -p-cymene)Cl(picolinate)] is active against HeLa (drug concentration at which 50% of the cells are viable relative to the control (IC 50 ) = 82.0 μM) and human melanoma cells (FemX, IC 50 = 36.2 μM). 10 The possible reason for this behavior is that the [Ru(η 6 -p-cymene) Cl(picolinate)] accumulates in the deoxyribonucleic acid (DNA) molecule, since it has high affinity for DNA-binding.…”

Section: Introductionmentioning

confidence: 99%

New Heteroleptic RuII/Diphosphine Complexes with Cytotoxicity against Human Breast and Murine Ascitic Sarcoma 180 Tumor Cells

Lima¹,

Corrêa²,

Graminha³

et al. 2020

J. Braz. Chem. Soc.

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The preparation, characterization, theoretical calculations and biological application of four Ru II complexes with 2-picolinate (pic), 2,2'-bipyridine (bipy) and P-P as ligands [P-P = 1,1-bis(diphenylphosphino)methane (dppm-1), 1,2-bis(diphenylphosphino)ethane (dppe-2), 1,3-bis(diphenylphosphino)propane (dppp-3) or 1,1'-bis(diphenylphosphino)ferrocene (dppf-4)], is here presented. The complexes 1-4, with general formula [Ru(pic)(P-P)(bipy)]PF 6 , were characterized by elemental analysis and by infrared (IR), UV-Vis, nuclear magnetic resonance (NMR 1 H and 13 P{ 1 H}) spectroscopies, cyclic voltammetry and X-ray crystallography technique. Additionally, preliminary in vitro tests against human breast (MDA-MB-231) and murine ascitic sarcoma 180 (S180) tumor cell lines were carried out, and compared with cisplatin, a reference drug. The drug concentration at which 50% of the cells are viable relative to the control (IC 50) values found for complexes 1, 2, 3 and 4 against MDA-MB-231 tumor cells were around 14.6, 7.6, 3.3 and 0.4 μM, respectively, while against S180 tumor cells these complexes showed IC 50 values of 71.9, 31.3, 11.2 and 3.5 μM, respectively. Therefore, the complexes were more active against MDA-MB-231 than S180.

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“…These toxic effects occur in both normal and cancer cells; therefore, the development of new molecules, which would overcome these disadvantages, is a priority (Ediriweera, Tennekoon, & Samarakoon, 2018). Several metal compounds with proven in vitro antitumor activity have been considered (Leon, Cadavid-Vargas, Di Virgilio, & Etcheverry, 2017;Liang et al, 2017;Markowska, Kasprzak, Jaszczynska-Nowinka, Lubin, & Markowska, 2015; Rozzo et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Vanadium compounds and cellular death mechanisms in the A549 cell line: The relevance of the compound valence

Guerrero-Palomo

Rendón-Huerta

Montaño

et al. 2018

J of Applied Toxicology

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Non‐small lung cell carcinoma has a high morbidity and mortality rates. The elective treatment for stage III and IV is cisplatinum that conveys serious toxic side effects. Vanadium compounds are metal molecules with proven antitumor activity that depends on its valence. Therefore, a better understanding of the mechanism of action of vanadium compounds is required. The aim of our study was to investigate the mechanisms of cell death induced by sodium metavanadate (NaVO3 [V(+5)]) and vanadyl sulfate (VOSO4 [(+4)]), both of which have reported apoptotic‐inducing activity. We exposed the A549 cell line to various concentrations (0‐100 μM) and to different exposure times to each compound and determined the cell viability and expression of caspases, reactive oxygen species (ROS) production, Bcl2, Bax, FasL and NO. Our results showed that neither compounds modified the basal expression of caspases or pro‐ and anti‐apoptotic proteins. The only change observed was the 12‐ and 14‐fold significant increase in ROS production induced by NaVO3 and VOSO4, respectively, at 100 μm concentrations after 48 hours. Our results suggest that classical apoptotic mechanisms are not related to the cell death induced by the vanadium compounds evaluated here, and showed that the higher ROS production was induced by the [(+4)] valence compound. It is possible that the difference will be secondary to its higher oxidative status and thus higher ROS production, which leads to higher cell damage. In conclusion, our results suggest that the efficacy of the cell death mechanisms induced by vanadium compounds differ depending on the valence of the compound.

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Recent development of transition metal complexes with in vivo antitumor activity

Cited by 89 publications

References 65 publications

Anticancer Ruthenium(III) Complexes and Ru(III)-Containing Nanoformulations: An Update on the Mechanism of Action and Biological Activity

Anticancer Ruthenium(III) Complexes and Ru(III)-Containing Nanoformulations: An Update on the Mechanism of Action and Biological Activity

New Heteroleptic RuII/Diphosphine Complexes with Cytotoxicity against Human Breast and Murine Ascitic Sarcoma 180 Tumor Cells

Vanadium compounds and cellular death mechanisms in the A549 cell line: The relevance of the compound valence

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