474448-87-8Relevant articles and documents
Bioinspired manganese(ii) complexes with a clickable ligand for immobilisation on a solid support
Chaignon, Jeremy,Stiriba, Salah-Eddine,Lloret, Francisco,Yuste, Consuelo,Pilet, Guillaume,Bonneviot, Laurent,Albela, Belen,Castro, Isabel
, p. 9704 - 9713 (2014/06/23)
Clickable ligands like N,N′-bis((pyridin-2-yl)methyl)prop-2-yn-1- amine (L1) and N-((1-methyl-1H-imidazol-2-yl)methyl)-N-(pyridin-2- ylmethyl)prop-2-yn-1-amine (L2) have been used to synthesise a series of manganese(ii) complexes for grafting onto appropriate solid supports. These ligands mimic the 2-His-1-carboxylate facial chelation present in the active site of the manganese-dependent dioxygenase (MndD), while the alkyne side function allows grafting of the ligand onto an azido-functionalised support using click chemistry methodologies. Such synthetic analogues of the MndD crystallise in the solid state as double halide or pseudohalide-bridged dinuclear manganese(ii) complexes of the general formula [Mn2(μ-X) 2X2L2] [L = L1 with X = Cl (1), Br (2), and N3 (3); L = L2 with X = N3 (4)]. Complexes 1-4 are characterised by a weak magnetic exchange interaction between the two high-spin MnII ions through the two X- bridges (J in the range of -0.059 to +5.30 cm-1, H = -J·S Mn1·SMn2 with SMn1 = SMn2 = 5/2). A new magneto-structural correlation of superexchange bis(μ 1,1-azido)dimanganese(ii) complexes has been proposed using both structural parameters, the Mn-N-Mn bridging angle and the Mn-Nazido distance. In MeOH-EtOH solution the dimeric species are present together with few percents of mononuclear manganese(ii) complexes as evidenced by electron paramagnetic resonance (EPR) spectroscopy. Grafting the complexes onto mesoporous silica of MCM-41 type stabilises both dimers and monomers in the nanopores of the solid.
Cytotoxic effect of (1-methyl-1H-imidazol-2-yl)-methanamine and its derivatives in PtII complexes on human carcinoma cell lines: A comparative study with cisplatin
Ferri, Nicola,Cazzaniga, Stefano,Mazzarella, Luca,Curigliano, Giuseppe,Lucchini, Giorgio,Zerla, Daniele,Gandolfi, Raffaella,Facchetti, Giorgio,Pellizzoni, Michela,Rimoldi, Isabella
, p. 2379 - 2386 (2013/05/09)
The synthesis and pharmacological characterisation of (1-methyl-1H- imidazol-2-yl)-methanamine and its derivatives in PtII complexes are described. Six out of eleven new PtII complexes showed a significant cytotoxic effect on NCI-H460 lung cancer cell line with EC50 values between 1.1 and 0.115 mM, determined by MTT assay. Compound Pt-4a showed a particularly more potent cytotoxic effect than the previously described Pt II complex with 2,2′-bipyridine, [Pt(bpy)Cl2], with an EC50 value equal to 172.7 μM versus 726.5 μM respectively, and similar potency of cisplatin (EC50 = 78.3 μM) in NCI-H460 cell line. The determination of the intracellular and DNA-bound concentrations of 195Pt, as marker of the presence of the complexes, showed that the cytotoxic compound Pt-4a readily diffused into the cells to a similar extent of cisplatin and directly interacted with the nuclear DNA. Pt-4a induced both p53 and p21Waf expression in NCI-H460 cells similar to cisplatin. A direct comparison of the cytotoxic effect between compound Pt-4a and cisplatin on 12 different cancer cell lines demonstrated that compound Pt-4a was in general less potent than cisplatin, but it had a comparable cytotoxic effect on non-small-cell lung cancer NCI-H460 cells, and the colorectal cancer cells HCT-15 and HCT-116. Altogether, these results suggested that the PtII complex with 1-methyl-1H-imidazol-2-yl)-methanamine (compound Pt-4a), displayed a significant cytotoxic activity in cancer cells. Similarly to cisplatin this compound interacts with nuclear DNA and induces both p53 and p21waf, and thus it represents an interesting starting point for future optimisation of new PtII complexes forming DNA adducts.
Anthranilamides and methods of their use
-
, (2008/06/13)
The present invention is related to anthranilamides of formula I, in which R(1) to R(7) have the meanings indicated herein, a process for their preparation, their use as medicaments, and pharmaceutical preparations containing them. The compounds act on the Kv1.5 potassium channel and inhibit a potassium current which is referred to as the ultra-rapidly activating delayed rectifier in the atrium of the human heart. The compounds are therefore suitable for use as novel antiarrhythmic agents for the treatment and prophylaxis of atrial arrhythmias (e.g., atrial fibrillation (AF) or atrial flutter).
Anthranilamides with heteroarylsulfonyl side chain, process of preparation, and use
-
, (2008/06/13)
This invention encompasses anthranilamides with heteroarylsulfonyl side chain, process for their preparation, their use as medicament or diagnostic aid, and pharmaceutical preparations containing them. Compounds of formula I, in which R1 to R7 have the meanings stated in the claims, act on the Kv1.5 potassium channel and inhibit a potassium current which is referred to as the ultra-rapidly activating delayed rectifier in the atrium of the human heart. They are therefore suitable as novel antiarrhythmic ingredients, such as for the treatment and prophylaxis of atrial arrhythmias, e.g. atrial fibrillation (AF) or atrial flutter.
