Photocytotoxic Activity of Copper(II) and Zinc(II) Complexes of Curcumin and (Acridinyl)dipyridophenazine

Copper(II) and zinc(II) beta-diketonates of N,N-donor ligands, viz. [Cu(dppz)(cur)](NO3) (1), [Cu(acdppz)(cur)](NO3) (2), [Cu(acdppz) (acac)](NO3) (3), [Zn(dppz)(cur)](NO3) (4) and [Zn(acdppz)(cur)] (NO3) (5), where dppz is dipyrido[3,2-a:2',3'-c]phenazine, acdppz is 11-(9-acridinyl)dipyrido[3,2-a:2',3'-c]phenazine, cur and acac are mono-deprotonated curcumin (Hcur) and acetyl acetone (Hacac), were synthesized, characterized and their photocytotoxicity studied. An analogue of complex 3, viz. [Cu(acdppz) (acac)(H2O)]Cl 1/2 (NO3) 1= 2 (3a), structurally characterized by X-ray crystallography, has a cationic complex in square-pyramidal geometry with CuN2O3 core with an axial aqua ligand. Complexes 1, 2, 4 and 5 displayed emission at similar to 520 nm (lambda(exc): 430 nm) in dimethyl sulfoxide (DMSO) giving a fluorescence quantum yield value within 0.01-0.06. The complexes, in contrast to free curcumin, were fairly stable in cellular media up to 36 h, with no apparent degradation of the bound curcumin. The complexes were photocytotoxic (IC50: 0.3 4.5 mu M) in human cervical cancer (HeLa), breast cancer (MCF-7) and liver cancer (HepG2) cells. The apoptotic cell death is due to reactive oxygen species formation. Complexes 2 and 5 showed significant uptake in HeLa cells, localizing predominantly in the cytoplasm. Mechanistic data from the pUC19 DNA photocleavage study suggest involvement of acridine and curcumin in photo-generation of singlet oxygen and hydroxyl radicals as the ROS in light of 400-700 nm.