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


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)=NH))Cl-2] (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(MeNH}Cu(pyrazine)Cu(LC(Me)=NH)(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 01. 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 jAM 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. (C) 2018 Elsevier Ltd. All rights reserved.




Chemistry; Crystallography


Bera, P; Brandao, P; Mondal, G; Santra, A; Jana, A; Mokhamatam, RB; Manna, SK; Mandal, TK; Bera, P

nossos autores


We gratefully acknowledge the Council for Scientific and Industrial Research (CSIR), Government of India for the project grant (No. 1(2858)/16/EMR-II). Panskura Banamali College acknowledges the grants that were received from the Department of Science and Technology (DST), Govt. of India through the FIST program (SR/FIST/college-295 dt.18.11.2015). We are also thankful to Dr. Debabrata Maity, Department of Chemistry, Indian Institute of Technology, Bombay, India and Dr. Santanu Pattanayak of National Chemical Laboratory, Pune, India for spectroscopy study.

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