Ru(ii)arene(N^N Bpy/phen)-based RAPTA Complexes for Anti-tumour Activity in Human Glioblastoma Cancer Cell Lines and Toxicity Studies in a Zebrafish Model

Overview

Journal RSC Adv

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2022 Jul 25

PMID 35873312

Authors

Anuja P K

Binoy Kar

Nilmadhab Roy

Priyankar Paira

Affiliations

Soon will be listed here.

Abstract

Herein, we have introduced a series of half-sandwich Ru(ii)arene(N^N bpy/phen)-based RAPTA complexes for brain cancer therapy. Among all the synthesized complexes, [(η--cymene)Ru(κ-,-4,7dimethyl phenanthroline)(PTA)]·2PF (4c) and [(η--cymene)Ru(κ-,-4,7diphenyl phenanthroline)(PTA)]·2PF (4d) showed outstanding potency against the T98G, LN229 and U87MG cancer cells. The antiproliferative activity of these complexes was reinforced by neurosphere, DNA intercalation, agarose gel electrophoresis, cell cycle analysis and time-dependent ROS detection assays. The real-time reverse transcription (RT)-polymerase chain reaction (PCR) study showed that complex 4c inhibited the TNF-α-induced NF-κB phosphorylation in glioma cells. Moreover, the biodistribution of complex 4c in different organs and the morphological patterns of widely used zebrafish embryos due to toxic effects have been evaluated.

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References

Hartinger C, Dyson P . Bioorganometallic chemistry--from teaching paradigms to medicinal applications. Chem Soc Rev. 2009; 38(2):391-401. DOI: 10.1039/b707077m. View

Bergamo A, Pelillo C, Chambery A, Sava G . Influence of components of tumour microenvironment on the response of HCT-116 colorectal cancer to the ruthenium-based drug NAMI-A. J Inorg Biochem. 2017; 168:90-97. DOI: 10.1016/j.jinorgbio.2016.11.031. View

Sangabathuni S, Murthy R, Madhukar Chaudhary P, Subramani B, Toraskar S, Kikkeri R . Mapping the Glyco-Gold Nanoparticles of Different Shapes Toxicity, Biodistribution and Sequestration in Adult Zebrafish. Sci Rep. 2017; 7(1):4239. PMC: 5484690. DOI: 10.1038/s41598-017-03350-3. View

Liu H, Sadler P . Metal complexes as DNA intercalators. Acc Chem Res. 2011; 44(5):349-59. DOI: 10.1021/ar100140e. View

Hurley L . DNA and its associated processes as targets for cancer therapy. Nat Rev Cancer. 2002; 2(3):188-200. DOI: 10.1038/nrc749. View

Mostafizar M, Cortes-Perez C, Snow W, Djordjevic J, Adlimoghaddam A, Albensi B . Challenges with Methods for Detecting and Studying the Transcription Factor Nuclear Factor Kappa B (NF-κB) in the Central Nervous System. Cells. 2021; 10(6). PMC: 8228352. DOI: 10.3390/cells10061335. View

Shakil M, Parveen S, Rana Z, Walsh F, Movassaghi S, Sohnel T . High Antiproliferative Activity of Hydroxythiopyridones over Hydroxypyridones and Their Organoruthenium Complexes. Biomedicines. 2021; 9(2). PMC: 7912191. DOI: 10.3390/biomedicines9020123. View

Fu X, Liu D, Lin Y, Hu W, Mao Z, Le X . Water-soluble DNA minor groove binders as potential chemotherapeutic agents: synthesis, characterization, DNA binding and cleavage, antioxidation, cytotoxicity and HSA interactions. Dalton Trans. 2014; 43(23):8721-37. DOI: 10.1039/c3dt53577k. View

Mandal P, Kundu B, Vyas K, Sabu V, Helen A, Singh Dhankhar S . Ruthenium(ii) arene NSAID complexes: inhibition of cyclooxygenase and antiproliferative activity against cancer cell lines. Dalton Trans. 2017; 47(2):517-527. DOI: 10.1039/c7dt03637j. View

10.

Thota S, Rodrigues D, Crans D, Barreiro E . Ru(II) Compounds: Next-Generation Anticancer Metallotherapeutics?. J Med Chem. 2018; 61(14):5805-5821. DOI: 10.1021/acs.jmedchem.7b01689. View

11.

Parveen S, Hanif M, Leung E, Tong K, Yang A, Astin J . Anticancer organorhodium and -iridium complexes with low toxicity in vivo but high potency in vitro: DNA damage, reactive oxygen species formation, and haemolytic activity. Chem Commun (Camb). 2019; 55(80):12016-12019. DOI: 10.1039/c9cc03822a. View

12.

Das U, Kar B, Pete S, Paira P . Ru(ii), Ir(iii), Re(i) and Rh(iii) based complexes as next generation anticancer metallopharmaceuticals. Dalton Trans. 2021; 50(32):11259-11290. DOI: 10.1039/d1dt01326b. View

13.

McQuitty R . Metal-based drugs. Sci Prog. 2014; 97(Pt 1):1-19. PMC: 10365534. DOI: 10.3184/003685014X13898980185076. View

14.

Cloughesy T, Cavenee W, Mischel P . Glioblastoma: from molecular pathology to targeted treatment. Annu Rev Pathol. 2013; 9:1-25. DOI: 10.1146/annurev-pathol-011110-130324. View

15.

Hanif M, Arshad J, Astin J, Rana Z, Zafar A, Movassaghi S . A Multitargeted Approach: Organorhodium Anticancer Agent Based on Vorinostat as a Potent Histone Deacetylase Inhibitor. Angew Chem Int Ed Engl. 2020; 59(34):14609-14614. DOI: 10.1002/anie.202005758. View

16.

Schatzschneider U, Metzler-Nolte N . New principles in medicinal organometallic chemistry. Angew Chem Int Ed Engl. 2006; 45(10):1504-7. DOI: 10.1002/anie.200504604. View

17.

Pena B, Saha S, Barhoumi R, Burghardt R, Dunbar K . Ruthenium(II)-Polypyridyl Compounds with π-Extended Nitrogen Donor Ligands Induce Apoptosis in Human Lung Adenocarcinoma (A549) Cells by Triggering Caspase-3/7 Pathway. Inorg Chem. 2018; 57(20):12777-12786. DOI: 10.1021/acs.inorgchem.8b01988. View

18.

Patel A, Tirosh I, Trombetta J, Shalek A, Gillespie S, Wakimoto H . Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 2014; 344(6190):1396-401. PMC: 4123637. DOI: 10.1126/science.1254257. View

19.

P K A, Roy N, Das U, Varddhan S, Sahoo S, Paira P . [Ru(η--cymene)(N^O 8-hydroxyquinoline)(PTA)] complexes as rising stars in medicinal chemistry: synthesis, properties, biomolecular interactions, anti-tumor activity toward human brain carcinomas, and biodistribution and toxicity in a zebrafish...]. Dalton Trans. 2022; 51(21):8497-8509. DOI: 10.1039/d2dt00666a. View

20.

Roy N, Sen U, Moharana P, Babu L, Kar B, Vardhan S . 2,2'-Bipyrimidine-based luminescent Ru(ii)/Ir(iii)-arene monometallic and homo- and hetero-bimetallic complexes for therapy against MDA-MB-468 and caco-2 cells. Dalton Trans. 2021; 50(34):11725-11729. DOI: 10.1039/d1dt01556g. View