137364-92-2Relevant academic research and scientific papers
Insights into the antiproliferative mechanism of (C^N)-chelated half-sandwich iridium complexes
Ramos, Robin,Zimbron, Jérémy M.,Thorimbert, Serge,Chamoreau, Lise-Marie,Munier, Annie,Botuha, Candice,Karaiskou, Anthi,Salmain, Michèle,Sobczak-Thépot, Jo?lle
supporting information, p. 17635 - 17641 (2020/12/30)
Transition metal-based anticancer compounds, as an alternative to platinum derivatives, are raising scientific interest as they may present distinct although poorly understood mechanisms of action. We used a structure-activity relationship-based methodology to investigate the chemical and biological features of a series of ten (C^N)-chelated half-sandwich iridiumIII complexes of the general formula [IrCp?(phox)Cl], where (phox) is a 2-phenyloxazoline ligand forming a 5-membered metallacycle. This series of compounds undergoes a fast exchange of their chlorido ligand once solubilised in DMSO. They were cytotoxic to HeLa cells with IC50 values in the micromolar range and induced a rapid activation of caspase-3, an apoptosis marker. In vitro, the oxidative power of all the complexes towards NADH was highlighted but only the complexes bearing substituents on the oxazoline ring were able to produce H2O2 at the micromolar range. However, we demonstrated using a powerful HyPer protein redox sensor-based flow cytometry assay that most complexes rapidly raised intracellular levels of H2O2. Hence, this study shows that oxidative stress can partly explain the cytotoxicity of these complexes on the HeLa cell line and gives a first entry to their mechanism of action. This journal is
Synthesis and evaluation of the anti parasitic activity of aromatic nitro compounds
Lopes, Marcela S.,De Souza Pietra, Renata C.C.,Borgati, Tatiane F.,Romeiro, Carla F.D.,Júnior, Policarpo A.S.,Romanha, Alvaro J.,Alves, Ricardo J.,Souza-Fagundes, Elaine M.,Fernandes, Ana Paula S.M.,De Oliveira, Renata B.
experimental part, p. 5443 - 5447 (2011/12/15)
A series of nitroaromatic compounds was synthesized and evaluated as potential antileishmanial and trypanocidal agents. Five compounds exerted significant anti-leishmanial activity in vitro against promastigotes forms of Leishmania (L.) amazonensis, with
Antibody catalyzed hydrolysis of enol ethers
Reymond, Jean-Louis,Jahangiri, Guiti K.,Stoudt, Catherine,Lerner, Richard A.
, p. 3909 - 3917 (2007/10/02)
The hydrolysis of alkyl enol ethers to their corresponding carbonyl compounds proceeds by rate determining protonation of the β-carbon to form an activated oxocarbonium ion intermediate and is catalyzed by acids (Kresge, A. J.; Chiang, Y. J. Chem. Soc. B 1967, 53). It can be catalyzed by antibodies with very high enantioselectivity of protonation at the β-carbon to form optically pure carbonyl compounds (Reymond, J.-L.; Janda, K. D.; Lerner, R. A. J. Am. Chem. Soc. 1992, 114, 2257). In the present study, the pH profile of the antibody 14D9 (anti-1) catalyzed, enantioselective hydrolysis of enol ether 4 between pH = 3.1 and pH = 7.2 has been measured in both H2O and D2O at 20°C. The kinetic solvent isotope effect is (kH/kD)cat = 1.75 for the antibody catalyzed reaction and (kH/kD)uncat = 1.92 for the background reaction. The Michaelis-Menten constant Km for substrate 4 changes from 35 μM at low pH to 190 μM. at high pH. Saturation of the catalytic activity is observed at low pH. These observations are consistent with general acid catalysis by an ionizable side chain with pK = 5.2, presumably a carboxyl group, in the active site. A maximum rate acceleration kcat/kuncat = 8200 is obtained at the high pH end of the profile, and a maximum turnover number of 9.75 × 10-5 s-1 is obtained at the low pH end. Enol ethers 15-21 are also catalytically hydrolyzed by 14D9. The maximum turnover numbered measured is 0.39 s-1 with 17 at pH = 6.0 at 20°C. The catalytic effect kcat/kuncat is influenced by the structure of the enol ether. Catalysis increases by a factor of 12 between 15 and its β-methyl analog 4 and by a factor of 34 between the six-membered ring enol ether 19 and its five-membered ring analog 17. These rate effects may reflect the principle of strain in catalysis. They suggest that hydrophobic interactions directly participate in transition-state stabilization, which is unexpected for an acid-base reaction usually discussed in terms of proton relay mechanisms. The implication of these findings for the design and improvement of antibody catalysts is discussed.
