Synthesis, Molecular Docking, DNA Binding and Anticancer Studies of Transition Metal Complex of N'-[Phenylmethylidene]-1,3-Benzothiazole-2-Carbohydrazone
Posted: 4 Feb 2020
Date Written: February 1, 2020
Deoxyribonucleic acid (DNA) is the molecular target for a number of clinically useful anticancer and antimicrobial drugs. Metallointercalators are the most extensively studied group of molecules as DNA intercalators. Transition metals complexed with aromatic organic compounds that can make a significant Arene-nucleobase stacking interaction can have a considerable antimicrobial and anticancer activity. In the present work we report design, synthesis, molecular docking, cytotoxicity and DNA binding studies of N'-[Phenylmethylidene]-1,3-benzothiazole-2-carbohydrazone (PMBC) and its Cu(II), Ni(II), Co(II) and Zn(II) metal complexes. The quantum chemical calculations of the title compounds were carried out using HyperChem 7.5 to obtain eigen values for molecular orbitals (HOMO and LUMO) of geometry optimized molecular structure of ligand. The computed data is informative to understand possible donor sites in PMBC that can bind with metal ions in the formation of metal complexes. The synthesized complexes were characterized by various spectro-analytical techniques and plausible structure was elucidated. Autodock 4.0 was used to dock the metal complexes into the interacalative site of DNA, and there binding affinity were estimated which were further determined experimentally by Absorption and Fluorescence studies with CT-DNA. The Kb values estimated by both absorption and fluorescence titrations were in good agreement and follow the order Zn(II)-PMBC > Ni(II) PMBC > Cu(II) PMBC > Co(II)-PMBC. Experimental binding affinity values were also corroborating with molecular docking results which provided further evidence of intercalation. Antitumor activity of ligand and its corresponding complexes against Hela Cervical cancer cell line by MTT reduction assay revealed zinc complex exhibits more anti-proliferative activity than PMBC and other complexes.
Keywords: Hydrazone and its complexes, DNA binding, Antitumor activity, Antimicrobial activity, Docking
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