52462-29-0Relevant articles and documents
A new photoactivatable ruthenium(II) complex with an asymmetric bis-thiocarbohydrazone: Chemical and biological investigations
Alinovi, Rossella,Bisceglie, Franco,Orsoni, Nicolò,Pelosi, Giorgio,Pinelli, Silvana,Pioli, Marianna,Scaccaglia, Mirco
, (2021)
The synthesis, photoactivation and biological activity of a new piano-stool Ru(II) complex is herein reported. The peculiarity of this complex is that its monodentate ligand which undergoes the photodissociation is an asymmetric bis-thiocarbohydrazone ligand that possesses a pyridine moiety binding to Ru(II) and the other moiety contains a quinoline that endows the ligand with the capacity of chelating other metal ions. In this way, upon dissociation, the ligand can be released in the form of a metal complex. In this article, the double ability of this new Ru(II) complex to photorelease the ligand and to chelate copper and nickel is explored and confirmed. The biological activity of this compound is studied in cell line A549 revealing that, after irradiation, proliferation inhibition is reached at very low half maximal inhibitory concentration (IC50) values. Further, biological assays reveal that the dinuclear complex containing Ni is internalized in cells.
Design, synthesis and in vitro bioactivity of mixed ligand Ru(II) complexes bearing the fluoroquinolone antibacterial agents
Pulipaka, Ramadevi,Dash, Soumya R.,Khanvilkar, Priyanka,Jana, Sarmita S.,Devkar, Ranjitsinh V.,Chakraborty, Debjani
, p. 721 - 735 (2019)
Mixed ligand Ru(II) phenanthroline complexes of the type [Ru(1,10-phen)2Flq]ClO4 (RPFlq-1-3) and “piano-stool”-type Ru(II) arene complexes [Ru(η6-p-cymene)Cl(Flq)] (RAFlq-1-3), where Flq = fluoroquinolone, have been synthesized, characterized and studied for their anticancer potential. DFT calculations were in line with the proposed structures, wherein the fluoroquinolones are coordinated to the metal through the ring carbonyl and one of the carboxylic oxygen?atoms in a bidentate fashion. Binding efficacies of the synthesized complexes with bovine serum albumin (BSA) and CT-DNA were studied spectroscopically, and it has been established that the arene complexes, though have moderate binding propensities to CT-DNA (Kb = 0.8–1.7 × 103?M?1), have 102–103-fold better binding efficacies toward BSA (Ka = 3.2 × 105–2.1 × 106?M?1) due to the presence of the hydrophobic arene moiety. These results further prompted a study in their in vitro cytotoxicity assay on A-549 non-small cell lung cancer and MCF7 breast cancer cell lines. Furthermore, gene expression studies on BAX and BCL-2 genes and FACS analysis confirmed apoptosis as the mode of cell death.
Evaluation of biomolecular interactions and cytotoxic activity of organometallic binuclear Ru(II) complexes of ferrocenyl thiosemicarbazones
Khanvilkar, Priyanka,Dash, Soumya R.,Vohra, Alisagar,Devkar, Ranjitsinh,Chakraborty, Debjani
, p. 6044 - 6055 (2021)
Four new ferrocenyl substituted thiosemicarbazone ligands (L1–L4) and their corresponding binuclear ruthenium(II) arene complexes of the general type [(η6-p cym)(L)Ru(μ-im)Ru(L)(η6-p-cym)]Cl (C1–C4) and [(η6-p cym)(L)Ru(μ-azpy)Ru(L)(η6-p-cym)]Cl2 (C5–C8) (cym = cymene, im = imidazole, azpy = 4,4′-azopyridine) have been synthesized and characterized. The structures of the complexes were established through DFT calculations and geometry optimization. The interactions of the binuclear complexes with DNA were investigated by absorption, emission and viscosity studies which indicated that the complexes bind to DNA via intercalation. Meanwhile, the interaction of complexes with the protein, bovine serum albumin (BSA), has also been studied using fluorescence emission spectroscopy. The experimental results show that the binuclear complexes exhibit good binding propensities to BSA. The complexes can quench the intrinsic fluorescence of BSA remarkably through a static or dynamic quenching process. In addition, the in?vitro cytotoxicity of complexes C1–C8 against HeLa cell line was assayed which showed lower IC50 values indicating their higher cytotoxicity and potency in killing the cancer cells at low concentrations. Communicated by Ramaswamy H. Sarma.
Mixed ligand ruthenium arene complexes containing N-ferrocenyl amino acids: Biomolecular interactions and cytotoxicity against MCF7 cell line
Ramadevi, Pulipaka,Singh, Rinky,Jana, Sarmita S.,Devkar, Ranjitsinh,Chakraborty, Debjani
, p. 80 - 87 (2017)
Synthesis, characterization, DNA and protein binding as well as anticancer activity of the organometallic complexes [Ru(η6-p-cym)(L)Cl] (where, p-cym?=?p-cymene MeC6H4Pri, L?=?N-ferrocenyl amino acid conjugates) RAFcA 1–4 have been described. The complexes 1–4 exhibited strong DNA/BSA binding and anticancer activity against breast cancer MCF7 cell line. Their binding with calf thymus DNA (CT DNA) and bovine serum albumin (BSA) have been examined by absorption and emission spectral studies. Strong interactions between complexes and CT-DNA have been affirmed by absorption spectral and EB displacement studies, while interaction with BSA via static quenching was explored by fluorescence titration. Cytotoxicity, apoptosis and in?vitro anticancer activity of 1–4 toward MCF7 cell line have been investigated by MTT assay. The IC50values (37.1?μM - 86.6?μM) were found to be distinctly lower than those of NAMI-A and RAPTA complexes for MCF7 cell line which was followed by gene expression studies to confirm apoptosis as the mode of cell death.
Anticancer activity of hydrogen-bond-stabilized half-sandwich Ru II complexes with heterocycles
Mitra, Raja,Das, Sangeeta,Shinde, Sridevi V.,Sinha, Sarika,Somasundaram, Kumaravel,Samuelson, Ashoka G.
, p. 12278 - 12291 (2012)
Neutral half-sandwich organometallic ruthenium(II) complexes of the type [(n6-cymene)RuCl2(L)] (H1-H10), where L represents a heterocyclic ligand, have been synthesized and characterized spectroscopically. The structures of five complexes were also established by single-crystal X-ray diffraction confirming a piano-stool geometry with n6 coordination of the arene ligand. Hydrogen bonding between the N-H group of the heterocycle and a chlorine atom attached to Ru stabilizes the metal-ligand interaction. Complexes coordinated to a mercaptobenzothiazole framework (H1) or mercaptobenzoxazole (H6) showed high cytotoxicity against several cancer cells but not against normal cells. In vitro studies have shown that the inhibition of cancer cell growth involves primarily G1-phase arrest as well as the generation of reactive oxygen species (ROS). The complexes are found to bind DNA in a non-intercalative fashion and cause unwinding of plasmid DNA in a cell-free medium. Surprisingly, the cytotoxic complexes H1 and H6 differ in their interaction with DNA, as observed by biophysical studies, they either cause a biphasic melting of the DNA or the inhibition of topoisomerase-IIα activity, respectively. Substitution of the aromatic ring of the heterocycle or adding a second hydrogen-bond donor on the heterocycle reduces the cytotoxicity. Copyright
The synthesis, structural characterization, and in vitro anti-cancer activity of chloro(p-cymene) complexes of ruthenium(II) containing a disulfoxide ligand
Huxham, Lynsey A.,Cheu, Elizabeth L.S.,Patrick, Brian O.,James, Brian R.
, p. 238 - 246 (2003)
Two diruthenium(II) complexes [RuCl2(p-cymene)]2(μ-BESE) (1), [RuCl2(p-cymene)]2(μ-BESP) (2), and the mononuclear salt [RuCl(p-cymene)(BESE)]PF6 (3), containing the disulfoxides BESE and BESP, were synthesized and characterized by elemental analysis, and NMR and IR spectroscopies, and were shown to contain S-bound sulfoxide groups; the disulfoxides are EtS(O)(CH2)nS(O)Et, where n=2 (BESE) or 3 (BESP). Complexes 1 and 3 were also characterized by X-ray crystallography. Preliminary in vitro tests of 1 and 3 were conducted using the MTT assay, which measures mitochondrial dehydrogenase activity as an indication of cell viability; these complexes showed in vitro anti-cancer activity against a human mammary cancer cell line (MDA-MB-435s) with IC50 values of 360 and 55 μM, respectively.
Selective Targeting of the Zinc Finger Domain of HIV Nucleocapsid Protein NCp7 with Ruthenium Complexes
Sheng, Yaping,Cao, Kaiming,Li, Ji,Hou, Zhuanghao,Yuan, Siming,Huang, Guangming,Liu, Hongke,Liu, Yangzhong
, p. 19146 - 19151 (2018)
Nucleocapsid protein 7 (NCp7) is an attractive target for anti-HIV drug development. Here we found that ruthenium complexes are reactive to NCp7 and various Ru-agents exhibit significantly different reactivity. Interestingly, the zinc-finger domains of NCp7 also demonstrate different affinity to Ru-complexes; the C-terminal domain is much more reactive than the N-terminal domain. Each zinc-finger domain of NCp7 binds up to three Ru-motifs, and the ruthenium binding causes zinc-ejection from NCp7 and disrupts the protein folding. Therefore, ruthenium complexes interfere with the DNA binding of NCp7 and interrupt the protein function. The different reactivity of Ru-agents suggests a feasible strategy for improving the targeting of NCp7 by ligand design. This work provides an insight into the mechanism of ruthenium complex with NCp7, and suggests more potential application of ruthenium drugs.
Antiparasitic activity and ultrastructural alterations provoked by organoruthenium complexes against: Leishmania amazonensis
Colina-Vegas, Legna,Lima Prado Godinho, Joseane,Coutinho, Thallita,Correa, Rodrigo S.,De Souza, Wanderley,Cola Fernandes Rodrigues, Juliany,Batista, Alzir Azevedo,Navarro, Maribel
, p. 1431 - 1439 (2019)
Four new organoruthenium complexes with formula [RuCl(η6-p-cymene)(μ-FCZ)]2[Cl]2 (1), [RuCl(FCZ)(η6-p-cymene)(PPh3)]PF6 (2), [RuCl(CTZ)(η6-p-cymene)(PPh3)]PF6 (3) and [RuCl(KTZ)(η6-p-cymene)(PPh3)]PF6 (4) (where FCZ: 2-(2,4-difluorophenyl)-1,3-di(1H-1,2,4-triazol-1-yl)-2-propanol, CTZ: 1-[(2-chlorophenyl)-diphenylmethyl-1H-imidazole] and KTZ: cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine) were synthesized, characterized and evaluated as potential inhibitors for Leishmania amazonensis growth by widely reported methods. Complexes 3 and 4 displayed effective IC50 activities against Leishmania amazonensis promastigotes and intracellular amastigotes in the range of nanomolar concentration. Scanning and transmission electron microscopy analysis of Leishmania amazonensis promastigotes after treatment with 300 or 500 nM of complexes 3 and 4 for 48 h showed morphological alterations in the cell surface, a shortening of the flagellum, loss of mitochondrial matrix, disorganization of the kDNA and abnormal chromatin condensation. Thus, our strategy of incorporating a ruthenium atom into the structure of clinical drugs to improve their efficacy continues to demonstrate suitability for metallodrug discovery purposes.
Cationic half-sandwich ruthenium (II) complexes ligated by pyridyl-triazole ligands: Transfer hydrogenation and mechanistic studies
Joseph, M. C.,Mapolie, S. F.,Swarts, A. J.
supporting information, (2021/11/30)
A series of novel cationic ruthenium half-sandwich complexes, bearing 1-substituted-4-pyridyl-1H-1,2,3-triazole ligands, were synthesized and fully characterized by a range of analytical techniques. The complexes were found to be efficient catalyst precursors for transfer hydrogenation reactions using ketones as substrates. We demonstrated that the complexes could hydrogenate acetophenone in excellent conversions (~75 %) within 3 h, employing a low concentration of base of only 2 mol %. Extending the reaction time to 6 h gave near quantitative conversions for both catalysts employed. In addition to this, the transfer hydrogenation of acetophenone was also found to proceed even at low catalyst loadings (0.025–0.05 mol%) and low base concentrations (0.25–1.0 mol%). Under these conditions substrate conversion was moderate (22–60 %). The catalytic efficiency of the most effective catalyst was then evaluated in the transfer hydrogenation of a small library of aromatic and aliphatic ketones. It was shown that more challenging substrates such as benzophenone and 2-octanone could be hydrogenated to the corresponding secondary alcohols in conversions > 90 %. Finally, based on several experimental observations, a possible mechanism for the process is proposed.