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Ferrocene conjugated copper(II) complexes of terpyridine and traditional Chinese medicine (TCM) anticancer ligands showing selective toxicity towards cancer cells
Author(s) -
Deka Banashree,
Bhattacharyya Arnab,
Mukherjee Sanjoy,
Sarkar Tukki,
Soni Kiran,
Banerjee Samya,
Saikia Kandarpa K.,
Deka Sasanka,
Hussain Akhtar
Publication year - 2018
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.4287
Subject(s) - chemistry , terpyridine , plumbagin , hela , moiety , cytotoxicity , stereochemistry , lawsone , conjugated system , ligand (biochemistry) , denticity , chelation , medicinal chemistry , in vitro , crystal structure , biochemistry , crystallography , metal , receptor , organic chemistry , genetics , biology , polymer
Six novel mixed‐ligand copper(II) complexes, namely, [Cu(R‐tpy)(L)]NO 3 ( 1–6 ), where R‐tpy is 4′‐phenyl‐2,2′:6′,2′′‐terpyridine (Ph‐tpy; 1–3 ) and 4′‐ferrocenyl‐2,2′:6′,2′′‐terpyridine (Fc‐tpy; 4–6 ), L is the bidentate O,O donor monoanion of plumbagin (5‐hydroxy‐2‐methyl‐1,4‐naphthoquinone; plum in 1 , 4 ), chrysin (5,7‐dihydroxyflavone; chry in 2 , 5 ) and curcumin (bis(4‐hydroxy‐3‐methoxyphenyl)‐1,6‐diene‐3,5‐dione; curc in 3 , 6 ) have been synthesized and characterized and their in vitro cytotoxicity against cancer cells is evaluated. The energy optimized structures and the frontier orbitals of the complexes have been obtained from the DFT calculations. Complexes 4–6 with a conjugated ferrocenyl moiety and TCM anticancer ligands, namely, plum (in 4 ), chry (in 5 ) and curc (in 6 ) showed potent cytotoxicity giving respective IC 50 values of 1.2 μM, 0.62 μM and 0.21 μM in HeLa and 2.0 μM and 1.0 μM and 0.34 μM in MCF‐7 cancer cells while being much less toxic to MCF‐10A normal cells (IC 50 : 8.3‐17.1 μM). In contrast, complexes 1–3 with a conjugated phenyl moiety were appreciably less toxic to HeLa cells with respective IC 50 values of 10.4 μM, 8.1 μM and 5.5 μM when compared with their ferrocenyl analogues 4–6 . Mechanistic studies using Hoechst staining and Annexin‐V‐FITC assays on cancer cells revealed an apoptotic pathway of cell death induced by the complexes. Fluorescence imaging study showed that complex 6 having curcumin as ligand localized primarily in the mitochondria of HeLa cells. Thus, we demonstrate in this study that ferrocene conjugation to copper(II) complexes of TCM anticancer ligands significantly increases the selectivity and cytotoxicity of the resulting complexes towards cancer cells over normal cells.