Synthesis, characterization, antitumor, and cytotoxic activity of mononuclear Ru(II) complexes (original) (raw)
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Development of Ru(II) Complexes: Next-Generation Anticancer Metallotherapeutics?
SYNERGY CONFERENCE-2017, CANCER PHARMACOLOGY RESEARCH, 2017
Cancers figure among the leading causes of death worldwide, accounting for 8.2 million deaths within five years of diagnosis. According to WHO report, it is expected that annual cancer cases will rise from 14 million in 2012 to 22 million within the next two decades. There is no curative therapy is available for the most forms of disseminated cancers, so that the discovery and development of novel active chemotherapeutic agents is largely needed. Metal compounds currently play a crucial role in medicinal chemistry and drug development after serendipitous discovery of blockbuster Platinum compounds. Platinum-based drug cisplatinis one of the most progressive and competently used medicament in the treatment of numerous forms of human cancers, but their therapeutic value can be minimized by serious side effects, and its effectiveness is diminished by acquired drug resistance.Searching for various alternative metal compounds several Ruthenium complexes as the substituents of cisplatin, possess numerous amicable properties suited to rational anticancer drug design and biological significance. The ruthenium-based complexes, which display ample promise in antiproliferation activity and diminished toxicity than platinum drugs, have been designed and developed in the last two decades. Ruthenium belongs to the same group of elements as iron, which is reflected by its robust affinity for transferrin and by the necessity of its reductive activation in cells. The development of antineoplastic ruthenium complexes has been of augmenting interest after RuIIIspecies, imidazolium-(imidazole) (dimethylsulfoxide)tetrachlororuthenate(III) (NAMI-A and indazolium transtetrachlorobis(1H-indazole)-ruthenate(III)] (KP1019) and KP1339 entered clinical trials.1 From the past one decade, many Ru(II) complexes bearing 1,10-phenanthroline and 2,2-bipyridine exert rather potent activities against selected tumor cells and other ruthenium complexes also reported as Protein Kinase Inhibitors.2 Our group efforts are focused on development of novel potent Ru(II) complex scaffolds bearing 1,10-phenanthroline, 2.2-bipyridine, Aromatic and Heterocyclic Thiosemicarbazone ligands.3 These scaffolds are chemically very robust and conformationally very rigid and thus may be a promising lead structure for further development. I am interested in exploring Ru(II) compounds as structural scaffolds for enzyme inhibition.
Synthesis, antineoplastic and cytotoxic activities of some mononuclear Ru (II) complexes
Journal of Enzyme Inhibition and Medicinal Chemistry, 2010
A series of mononuclear Ru(II) complexes of the type [Ru(S)(2)(K)](2+), where S = 1,10-phenanthroline/2,2'-bipyridine and K = 4-OH-btsz, 4-CH(3)-btsz, 3,4-di-OCH(3)-btsz, 4-OH-binh, 4-CH(3)-binh, 3,4-di-OCH(3)-binh, were prepared and characterized by elemental analysis, FTIR, (1)H-NMR, and mass spectroscopy. The complexes displayed metal-ligand charge transfer (MLCT) transitions in the visible region. These ligands formed bidentate octahedral ruthenium complexes. The title complexes were evaluated for their in vivo anticancer activity against a transplantable murine tumor cell line, Ehrlisch's ascites carcinoma (EAC), and in vitro cytotoxic activity against human cancer cell lines Molt 4/C(8) and CEM and murine tumor cell line L1210. The ruthenium complexes showed promising biological activity especially in decreasing tumor volume and viable ascites cell counts. Treatment with these complexes prolonged the life span of mice bearing EAC tumors by 10-52%. In vitro evaluation of these ruthenium complexes revealed cytotoxic activity from 0.21 to 24 muM against Molt 4/C(8), 0.16 to 19 microM against CEM, and 0.75 to 32 microM against L1210.
Ruthenium anticancer compounds: Challenges and expectations
Chimia, 2007
Tw o ruthenium compounds, namely [ImH]trans-[RuCl 4 (Im)(dmso-S)] (NAMI-A, Im = imidazole) and [IndH] trans-[RuCl 4 (Ind) 2 ] (KP1019, Ind = indazole) have already completed phase I clinical trials as anticancer agents. They both have properties different from platinum anticancer drugs: for example, NAMI-A is selectively active against metastases of solid tumors. They show that in the field of anticancer metal drugs a new approach, based on targeted therapies, is possible. After a concise history of ruthenium anticancer compounds, this contribution will focus on ruthenium-dmso complexes and, in particular, on NAMI-A. Particular emphasis is given on the challenges that are inherent to this field: how to develop new anticancer ruthenium compounds and how to select new active compounds that manifest their anticancer activity through non-conventional mechanisms.
The synthesis and spectroscopic characterization of ruthenium complexes (R-1 to R-8) of the type [Ru(A) 2 (B)], (where A = 1,10-phenanthroline/2,2 0 -bipyridine and B = 3,4,5-tri-OCH 3 -DPC, 4-CH 3 -DPC, 4-N-(CH 3 ) 2 -DPC, 4-NO 2 -DPC are described. These ligands form bidentate octahedral ruthenium complexes. The title complexes were subjected to in vitro cytotoxic activity measurements against the human cancer T-lymphocyte cell lines MTT assay. In vitro evaluation of these ruthenium complexes revealed cytotoxic activity from 0.24 to 1.4 mg/mL against CEM, 0.44 to 1.9 mg/mL against Molt4/C8, 0.28 to 1.5 mg/mL against L1210, 0.24 to 0.98 mg/mL against HL60, and 0.25 to 1.2 mg/mL against BEL7402, depending the nature of the compound.
SYNTHESIS, CHARACTERIZATION AND CYTOTOXIC ACTIVITY OF SOME Ru (II) COMPLEXES
Turkish Journal of Pharmaceutical Sciences, 2011
The synthesis and characterization of ruthenium complexes (Ru1–Ru8) of the type [Ru(S)2(K)], (where S = 1,10-phenanthroline/ 2,2’-bipyridine and K = iinh, inhba, na, mitsz) are described. These ligands form bidentate octahedral ruthenium complexes. The title compounds were subjected to in vitro cytostatic activity measurements against the human cancer T-lymphocyte cell lines Molt 4/C8 and CEM, and the murine tumor leukemia cell line L1210. In vitro evaluation of these ruthenium compounds revealed cytotoxic activity from 0.84 to 119 µg/mL against CEM, 3.7 to 158 µg/mL against Molt and 15 to ≥200 µg/mL against L1210 cell proliferation, depending the nature of the compound.
Ruthenium(II) Complexes as Potential Apoptosis Inducers in Cancer Therapy
Serbian Journal of Experimental and Clinical Research, 2019
The compound cis-diamminedichloroplatinum(II) (cisplatin) is the most widely used anticancer drug, but due to its serious side effects (including gastrointestinal symptoms, renal tubular injury, neuromuscular complications, and ototoxicity), clinical applications of cisplatin are limited. Therefore, these limitations have provided an encouragement for further research into other transition metal complexes, with an aim to overcome the disadvantages related with cisplatin therapy. In the search for effective complexes that can be targeted against tumor cells, many research groups synthesized various ruthenium( II) complexes with different ligands. Also, newly synthesized ruthenium(II) complexes showed selective anticancer activity against different types of cancer cells. Activity of ruthenium(II) complexes in some cases was even higher than that of cisplatin against the same cells. Precise mechanism of action of ruthenium(II) complexes is not fully understood. The different examples m...
Journal of the Brazilian Chemical Society, 2015
The synthesis, characterization and cytotoxic activity of cis-[Ru(dicl)(dppm) 2 ]PF 6 and cis-[Ru(ibu)(dppm) 2 ]PF 6 , (dppm = 1,1-bis(diphenylphosphine)methane; dicl = diclofenac anion and ibu = ibuprofen anion), are described in this work. Complexes were characterized by elemental analysis, Fourier transform infrared spectroscopy (FTIR), UV-Vis, 31 P{ 1 H} nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRESIMS). X-ray structure of cis-[Ru(ibu)(dppm) 2 ]PF 6 is also described. Preliminary calf thymus DNA (ct-DNA) binding studies were carried out by UV-Vis and viscosity experiments, with results suggesting the existence of electrostatic interactions between ruthenium complexes and ct-DNA. Cytotoxicity assays were carried out on a panel of human cancer cell lines and a human normal cell line. Complexes displayed a high to moderate cytotoxicity with IC 50 ranging from 5 to 47 µmol L-1. cis-[Ru(ibu) (dppm) 2 ]PF 6 was found to be the most active, with IC 50 values lower than cisplatin. The degree of cytotoxicity was maintained for the normal cell line, although cis-[Ru(ibu)(dppm) 2 ]PF 6 exhibited a similar selectivity to that of cisplatin but with a higher activity for at least two tumor cell lines which evidences a promising anticancer candidate and selects this complex for further experiments.