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In vitro anti‐proliferative and in silico docking studies of heteroleptic copper(II) complexes of pyridazine‐based ligands and ciprofloxacin
Author(s) -
Rafi U. Muhammed,
Mahendiran D.,
Kumar R. Senthil,
Rahiman A. Kalilur
Publication year - 2019
Publication title -
applied organometallic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.53
H-Index - 71
eISSN - 1099-0739
pISSN - 0268-2605
DOI - 10.1002/aoc.4946
Subject(s) - chemistry , pyridazine , hela , docking (animal) , copper , mtt assay , octahedral molecular geometry , cytotoxicity , stereochemistry , in vitro , crystallography , biochemistry , organic chemistry , crystal structure , medicine , nursing
Three heteroleptic copper(II) complexes of the type [Cu(L 1–3 )(cf)(ClO 4 )] ( 1 – 3 ), where cf = ciprofloxacin, have been synthesized using pyridazine‐based ligands 3‐chloro‐6‐(salicylidenehydrazinyl)pyridazine (HL 1 ), 3‐chloro‐6‐(4‐diethylaminosalicylidenehydrazinyl)pyridazine (HL 2 ) and 3‐chloro‐6‐(5‐bromosalicylidenehydrazinyl)pyridazine (HL 3 ). Electronic spectral data and magnetic moment values suggest octahedral geometry for the synthesized copper(II) complexes. Electrochemical data of the copper(II) complexes present an irreversible one‐electron reduction wave in the cathodic potential region ( E pc ) between −0.631 and −0.670 V. Frontier molecular orbital calculations were carried out, and the obtained low‐energy gap supports the bio‐efficacy of the complexes. All the complexes were screened for their in vitro cytotoxicity activity against three human cancerous (breast adenocarcinoma (MCF‐7), hepatoma (HepG‐2) and cervical (HeLa)) and one non‐cancerous (non‐tumorigenic human dermal fibroblast (NHDF)) cell lines using MTT assay, in which complex 2 exhibited higher activity. The apoptosis induction by the complexes was analysed using the Hoechst dye staining method with MCF‐7 cell line, which indicates higher apoptotic activity of complex 2 . A molecular docking study was carried out to ascertain the binding affinity of the synthesized heteroleptic copper(II) complexes with phosphoinositide 3‐kinase gamma (PI3Kγ) receptor.