An unusual iminoacylation of 2-amino pyridyl thiazole: Synthesis, X-ray crystallography and DFT study of copper(II) amidine complexes and their cytotoxicity, DNA binding and cleavage study

• Autor(a) principal: Bera, Pradip
• Data de Publicação: 2019
• Outros Autores: Brandão, Paula, Mondal, Gopinath, Santra, Ananyakumari, Jana, Abhimanyu, Mokhamatam, Raveendra Babu, Manna, Sunil Kumar, Mandal, Tarun Kanti, Bera, Pulakesh
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/36764
• topic: Pyridyl-thiazole; Amidine complexes; X-ray crystallography; Cytotoxicity; DNA cleavage

Insertion of acetonitrile in the exocyclic NH2 group of the thiazole unit of 2-amino-4-(2-pyridyl)thiazole (HL) in the presence of copper chloride results in the formation of the monomeric amidine complex [Cu{LC(Me)double bondNH)}Cl2] (1). The same reaction of HL and copper(II) perchlorate yields the complex [Cu(HL)2](ClO4)2 (2), without acetonitrile insertion. However, the presence of a spacer donor, e.g. pyrazine, in the reaction medium results in the formation of a dinuclear amidine derivative, [(ClO4){LC(Me)double bondNH}Cu(μ-pyrazine)Cu{LC(Me)double bondNH}(ClO4)] (ClO4)2 (3). Complexes 1 and 3 are the first examples of copper assisted iminoacylation of 2-amino pyridylthiazole derivatives, confirming a nitrile to amidine transformation. The new complexes were characterized by single crystal X-ray crystallography, cyclic voltammetry and a DFT study. The complexes have a potential cytotoxic effect in human monocytic cells (U937) with IC50 values ranging from 0.84 to 4.5 μM. Significant necrotic activities are ascertained by a lactate dehydrogenase (LDH) enzyme release assay. The interaction with calf thymus (CT) DNA shows the binding constant (Kb) values are ∼104 M−1. The chemical nuclease activity of 1, 2 and 3 result in 65, 99 and 80% relaxation of supercoiled DNA at 10 μM in the presence of glutathione (GSH, 1 mM), respectively. The study with radical scavengers proved that a hydroxyl or singlet oxygen-like species is responsible for the DNA degradation.