Nickel(II) complexes [Ni(cur)(L)](OAc) (1-3) where L is N,N-donor heterocyclic bases namely 1,10-phenanthroline (phen in 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq in 2), dipyrido[3,2-a:2′,3′-c]phenazine (dppz in 3) and Hcur is curcumin were prepared, fully characterized and light-induced in vitro anticancer activity studied. Three nickel(II) complexes containing acetylacetonato (Hacac) ligand, viz.[Ni(acac)(L)](OAc) (4-6) where L is phen (in 4), dpq (in 5), dppz (in 6) were prepared and used as controls. Complex 4 was structurally characterized by single crystal X-ray diffraction technique, which revealed an octahedral NiNO geometry around the metal centre. Complexes 1-3 showed an intense curcumin-based band at ∼440 nm in DMSO-Tris-HCl buffer (pH = 7.2) (1:4 v/v) which masks the nickel based d-d band. The curcumin comlexes (1-3) were redox inactive at the nickel centre, whereas the acetylacetonato complexes (4-6) displayed an irreversible voltammetric response at ∼1.00 V vs. Ag/AgCl reference electrode in DMF. The complexes bind to calf thymus DNA (ct-DNA) with considerable affinity and interacted with human serum albumin (HSA) with moderate affinity. The Ni(II) curcumin complexes display significant in vitro light-induced cytotoxicity in HeLa (human cervical carcinoma) and A549 (lung cancer cells) involving reactive oxygen species (ROS), with very low dark toxicity. The complexes were found to be much less toxic to immortalized lung epithelial normal cells (HPL1D). Confocal microscopic images using complex 2 and 3 showed that they primarily localize in the cytosol of A549 cells. The mechanism of cell death is mainly apoptosis in nature showing arrest of sub-G1 phase of cell cycle progression in A549 cells under visible light exposure and involves significant loss of mitochondrial membrane potential as observed from JC-1 assay.
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References

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