Anticancer activity, DNA binding and docking study of M(II)-complexes (M = Zn, Cu and Ni) derived from a new pyrazine-thiazole ligand: synthesis, structure and DFT


A series of structurally related Zn(II), Cu(II) and Ni(II) complexes of 4-(2-(2-(1-(pyrazin-2-yl)ethylidene)-hydrazinyl)-thiazol-4-yl)-benzonitrile (PyztbH) have been synthesized and characterized by spectroscopy, single crystal X-ray crystallography and density functional theory (DFT). All the complexes are mononuclear and the molecular composition of the complexes viz. [Zn(Pyztb)(2)] (1), [Zn(PyztbH)(SCN)(2)] (2), [Cu(Pyztb)(N-3)(MeOH)] (3) and [Ni(Pyztb)(PyztbH)]ClO4 (4) is confirmed by single crystal X-ray crystallography. The interaction of the compounds with calf thymus DNA (CTDNA) was studied by various spectroscopic methods (UV-Vis and fluorescence) and molecular docking study. Both the binding constant (k(b)) and the Stern-Volmer dynamic quenching constant (K-SV) values of the compounds are in the order of 10(4) indicating the intercalative binding mode of the compounds with CTDNA. The molecular docking study revealed that PyztbH, 1 and 3 are well fitted in the active sites of DNA having higher binding affinity than 2 and 4. All the synthesized compounds are assessed for anticancer activity towards different human cancer cell lines having different tissue origin e.g., U-937 (histiocytic lymphoma), HepG2 (hepatic carcinoma), HEK293T (embryonic kidney), U2OS (osteosarcoma), HeLa (cervical epithelium), A549 (lung carcinoma) and A431 (squamous carcinoma). The thiazole-pyrazine ligand shows relatively less cytotoxicity toward the tested cell lines than its metal derivatives. MTT assays reveal that 1 (IC50 values 1.5 to 21 mu M) and 3 (IC50 values 1.0 to 15 mu M) showed higher cytotoxicity than 2 (IC50 values 1.0 to 126 mu M) and 4 (IC50 values 9 to 106 mu M) across the cell types. Both 1 and 3 follow the necroptotic pathway of cell death, whereas 2 and 4 follow the apoptotic pathway. Peripheral blood mononuclear cell (PBMC) assay of 1, 2 and 4 revealed nontoxicity in normal blood cells.



subject category

Chemistry, Multidisciplinary


Bera, P; Aher, A; Brandao, P; Manna, SK; Bhattacharyya, I; Mondal, G; Jana, A; Santra, A; Bera, P

our authors


We gratefully acknowledge the Council for Scientific and Industrial Research (CSIR), Government of India, for financial support [grant no. 1(2858)/16/EMR-II]. Panskura Banamali College (Autonomous) acknowledges the grants received from the Department of Science and Technology (DST), Govt. of India, through the FIST program (No. SR-FIST-COLLEGE-295-dt18/11/2015).

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