New ruthenium(II)/phosphines/diimines complexes: Promising antitumor (human breast cancer) and Mycobacterium tuberculosis fighting agents

Santos, Edjane R. dos; Mondelli, Melina; Pozzi, Lucas V.; Corrêa, Rodrigo S.; Salistre-de-Araujo, Heloisa S.; Pavan, Fernando Rogério; Leite, Clarice Queico Fujimura; Ellena, Javier; Malta, V. R. S.; Machado, Sérgio P.; Batista, Alzir A.

doi:10.1016/j.poly.2013.01.004

Cited by 41 publications

(25 citation statements)

References 27 publications

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“…Lapachol was obtained according to the procedure described in [24]. The precursors cis-[RuCl 2 (PPh 3 ) 2 (X-bipy)] (X = H, methyl (Me) and methoxy (MeO)) and cis-[RuCl 2 (PPh 3 ) 2 (phen)] were prepared according to literature [26,27]. Typically The ruthenium(II) complexes with N-N = bipy(1), Me-bipy(2), MeO-bipy(3) and phen(4) were prepared by reacting an excess of lapachol ligand (0.137 mmol; 33.0 mg), previously dissolved in degassed mixture of CH 2 Cl 2 :MeOH (50:50) solvent, and the same equivalent of triethylamine Et 3 N, and the cis-[RuCl 2 (PPh 3 ) 2 (N-N)] precursors (0.114 mmol; ≅ 100.0 mg).…”

Section: Synthesismentioning

confidence: 99%

Antiparasitic activities of novel ruthenium/lapachol complexes

Barbosa

Corrêa

Oliveira

et al. 2014

Journal of Inorganic Biochemistry

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The present study describes the synthesis, characterization, antileishmanial and antiplasmodial activities of novel diimine/(2,2′-bipyridine (bipy), 1,10-phenanthroline (phen), 4,4′-methylbipyridine (Me-bipy) and 4,4′-methoxybipyridine (MeO-bipy)/phosphine/ruthenium(II) complexes containing lapachol (Lap, 2-hydroxy-3- The Ru(III) complex, [RuCl 2 (Lap)(dppb)], was also characterized by the EPR technique. The structure of the complexes [Ru(Lap)(PPh 3 ) 2 (bipy)]PF 6 and [RuCl 2 (Lap)(dppb)] was elucidated by X-ray diffraction. The evaluation of the antiparasitic activities of the complexes against Leishmania amazonensis and Plasmodium falciparum demonstrated that lapachol-ruthenium complexes are more potent than the free lapachol. The [RuCl 2 (Lap)(dppb)] complex is the most potent and selective antiparasitic compound among the five new ruthenium complexes studied in this work, exhibiting an activity comparable to the reference drugs.

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Section: Synthesismentioning

confidence: 99%

Antiparasitic activities of novel ruthenium/lapachol complexes

Barbosa

Corrêa

Oliveira

et al. 2014

Journal of Inorganic Biochemistry

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“…From the point of view of medicinal chemistry, ruthenium complexes have been explored as an alternative to platinum complexes in the context of anticancer and anti-infective chemotherapy (20)(21)(22). More specifically, ruthenium complexes are described as outstanding bioactive agents because of the phosphine ligands, which provide great stability for these compounds (23)(24)(25)(26). Nevertheless, only a few ruthenium complexes containing these ligands have been fully examined against T. cruzi (19).…”

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confidence: 99%

Nitro/Nitrosyl-Ruthenium Complexes Are Potent and Selective Anti-Trypanosoma cruzi Agents Causing Autophagy and Necrotic Parasite Death

Bastos

Barbosa

Silva

et al. 2014

Antimicrob Agents Chemother

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e cis-[RuCl(NO 2 )(dppb)(5,5=-mebipy)] (complex 1), cis-[Ru(NO 2 ) 2 (dppb)(5,5=-mebipy)] (complex 2), ct-[RuCl(NO)(dppb)(5,5=-mebipy)](PF 6 ) 2 (complex 3), and cc-[RuCl(NO)(dppb)(5,5=-mebipy)](PF 6 ) 2 (complex 4), where 5,5=-mebipy is 5,5=-dimethyl-2,2=-bipyridine and dppb is 1,4-bis(diphenylphosphino)butane, were synthesized and characterized. The structure of complex 2 was determined by X-ray crystallography. These complexes exhibited a higher anti-Trypanosoma cruzi activity than benznidazole, the current antiparasitic drug. Complex 3 was the most potent, displaying a 50% effective concentration (EC 50 ) of 2.1 ؎ 0.6 M against trypomastigotes and a 50% inhibitory concentration (IC 50 ) of 1.3 ؎ 0.2 M against amastigotes, while it displayed a 50% cytotoxic concentration (CC 50 ) of 51.4 ؎ 0.2 M in macrophages. It was observed that the nitrosyl complex 3, but not its analog lacking the nitrosyl group, releases nitric oxide into parasite cells. This release has a diminished effect on the trypanosomal protease cruzain but induces substantial parasite autophagy, which is followed by a series of irreversible morphological impairments to the parasites and finally results in cell death by necrosis. In infected mice, orally administered complex 3 (five times at a dose of 75 mol/kg of body weight) reduced blood parasitemia and increased the survival rate of the mice. Combination index analysis of complex 3 indicated that its in vitro activity against trypomastigotes is synergic with benznidazole. In addition, drug combination enhanced efficacy in infected mice, suggesting that ruthenium-nitrosyl complexes are potential constituents for drug combinations.

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“…The distances for the Ru-Cl, Ru-P and Ru-N bonds lengths and bond angles found for the compound is within the normal range for similar ruthenium(II) complexes. 12,25,27 In Figure 2A the six rings of the dpqQX ligand labeled (a-f) are depicted. Rings a and b are connected with the ruthenium(II), while rings c-f (tetraaza center) are in the outer-coordination sphere responsible for intermolecular interactions.…”

Section: P{mentioning

confidence: 99%

Polypyridyl Ruthenium Complexes: Novel DNA-Intercalating Agents against Human Breast Tumor

Barolli¹,

Corrêa²,

Miranda³

et al. 2017

J. Braz. Chem. Soc.

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This paper describes a new series of four DNA-intercalating agents with promising anticancer activities, based on ruthenium(II) with the planar ligand dpqQX (dpqQX = dipyrido[3,2-a:2',3'-c] quinoxaline [2,3-b] quinoxaline). The complexes identified as trans-[RuCl(dppb = 1,4-bis(diphenylphosphine)butane and PPh 3 = triphenylphosphine) were characterized by 31 P{ 1 H} nuclear magnetic resonance (NMR) and infrared spectroscopies, cyclic voltammetry, molar conductance measurements, elemental analysis, mass spectrometry and X-ray diffraction analysis for complex ct-[RuCl 2 (PPh 3 ) 2 (dpqQX)]. Their in vitro cytotoxic activities against MDA-MB-213 and MCF-7 breast cancer cells were evaluated and compared with normal L-929 cells. Low drug concentration at which 50% of the cells are viable relative to the control (IC 50 ) values were obtained for all four complexes compared with a reference metallodrug, cisplatin. In addition, DNA affinity studies from titrations, as well as the images obtained by atomic force microscopy (AFM) involving pBR322 plasmid DNA, suggest interactions between the metal complexes and the DNA macromolecule, in which they act as intercalating agents. The intercalation of the complexes with DNA was confirmed by viscosity measurements.

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New ruthenium(II)/phosphines/diimines complexes: Promising antitumor (human breast cancer) and Mycobacterium tuberculosis fighting agents

Cited by 41 publications

References 27 publications

Antiparasitic activities of novel ruthenium/lapachol complexes

Antiparasitic activities of novel ruthenium/lapachol complexes

Nitro/Nitrosyl-Ruthenium Complexes Are Potent and Selective Anti-Trypanosoma cruzi Agents Causing Autophagy and Necrotic Parasite Death

Polypyridyl Ruthenium Complexes: Novel DNA-Intercalating Agents against Human Breast Tumor

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