Cu(II) flavonoids as potential photochemotherapeutic agents.

Flavonoids, naturally derived polyphenolic compounds, have received significant attention due to their remarkable biochemical properties that offer substantial health benefits to humans. In this work, a series of six Cu(II) flavonoid complexes of the formulation [Cu(L1)(L2)](ClO4) where L1 is 3-hydroxy flavone (HF1, 1 and 4), 4-fluoro-3-hydroxy flavone (HF2, 2 and 5), and 2,6-difluoro-3-hydroxy flavone (HF3, 3 and 6); L2 is 1,10-phenanthroline (phen, 1-3) and 2-(anthracen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (aip, 4-6) were successfully synthesized, fully characterized and also evaluated for their in vitro photo-triggered cytotoxicity in cancer cells. The single-crystal X-ray diffraction structure of complex 2 shows square pyramidal geometry around the Cu(II) center. The complexes 1-6 showed quasi-reversible cyclic voltammetric responses for the Cu(II)/Cu(I) couple at ∼-0.230 V with a very large ΔEp value of ∼350-480 mV against the Ag/AgCl reference electrode in DMF-0.1 M tetrabutylammonium perchlorate (TBAP) at a scan rate of 50 mV s-1. The complexes were found to have considerable binding propensity for human serum albumin (HSA) and calf thymus DNA (ct-DNA). The complexes displayed remarkable dose-dependent photocytotoxicity in visible light (400-700 nm) in both A549 (human lung cancer) and MCF-7 (human breast cancer) cell lines while remaining significantly less toxic in darkness. They were found to be much less toxic to HPL1D (immortalized human peripheral lung epithelial) normal cells compared to A549 and MCF-7 cancer cells. Upon exposure to visible light, they generate reactive oxygen species, which are thought to be the main contributors to the death of cancer cells. In the presence of visible light, the complexes predominantly elicit an apoptotic mode of cell death. Complex 6 preferentially localizes in the mitochondria of A549 cells.

Visible light-induced cytotoxicity studies on Co(ii) complexes having an anthracene-based curcuminoid ligand.

Herein, two ternary cobalt(ii) complexes, namely [Co(9-accm)(phen)2](OAc) (1) and [Co(9-accm)(dppz)2](OAc) (2), where 9-accmH is 1,7-(di-9-anthracene-1,6-heptadiene-3,5-dione), phen is 1,10-phenanthroline and dppz is dipyrido[3,2-a:2',3'-c]phenazine, having an anthracene-based curcuminoid and phenanthroline bases were synthesized and fully characterized, and their in vitro photocytotoxicities were studied in cancer cells. To understand the role of the curcuminoid ligand 9-accm in photo-activated cytotoxicity, two control complexes, viz. [Co(dbm)(phen)2](OAc) (3) and [Co(dbm)(dppz)2](OAc) (4), where dbmH is 1,3-diphenyl-1,3-propanedione (dibenzoylmethane), were prepared and used for the control experiments. Complex 3 was structurally characterized by X-ray crystallography. The complexes displayed a quasi-reversible Co(i)/Co(ii) redox couple at ∼-1.1 V and an irreversible Co(ii)/Co(iii) couple at ∼1.3 V vs. Ag/AgCl in DMF-0.1 M [Bun4N](ClO4). Highly intense 9-accm ligand-centred bands were observed at ∼250-450 nm, which masked the Co(ii)-based weak d-d bands in the DMF-Tris-HCl buffer (1 : 9 v/v). The complexes displayed a significant binding propensity for calf-thymus (ct) DNA with binding constants in the range from (2.42 ± 0.10) × 105 to (3.24 ± 0.13) × 106 M-1. They also showed a moderate binding affinity for human serum albumin (HSA), displaying Kb values in the order of ∼104-105 M-1. The complexes 1 and 2 showed prodigious photoenhanced cytotoxicity in human cervical cancer (HeLa) and breast cancer (MCF-7 and MDA-MB-231) cells with low dark toxicity, whereas they were non-toxic to immortalized lung epithelial normal cells (HPL1D). Flow cytometric studies showed a time-dependent uptake of the complexes 1 and 2 in HeLa cells. The complexes generated reactive oxygen species (ROS) upon excitation with low energy visible light, thereby killing the cancer cells. The results from DAPI staining, AO/EB dual staining and Annexin-V-FITC experiments suggested that the complexes induce cell death primarily via an apoptotic mechanism in HeLa cells.