Remarkable photo-induced anticancer activity of vitamin-B6 Schiff base copper(II) complexes of pyridyl bases (original) (raw)
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2015
Vitamin-B6 (VB6) Schiff base (H2L) copper(II) complexes of pyridyl bases, viz. Cu(bpy)(L)] (1), Cu(phen)(L)] (2) and Cu(dppz)(L)] (3), where bpy is 2,2'-bipyridine, phen is 1,10-phenanthroline and dppz is dipyrido3,2-a:2',3'c]phenazine are synthesized, characterized and their phto-induced anticancer activity studied. The non-electrolytic one electron paramagnetic complexes exhibit a d-d band near 700 nm in DMF. The dppz complex intercalatively binds to calf-thymus DNA with binding constant (K-b) values of similar to 10(6) M-1. This complex exhibits low chemical nuclease activity but excellent DNA photocleavage activity when irradiated with red light of 705 nm forming (OH)-O-center dot radical. It displays remarkable photocytotoxicity in human cervical cancer cells (HeLa) giving IC50 value of 0.9 mu M in visible light (400-700 nm) while being less toxic in darkness (IC50 : 23 mu M). The cellular uptake of the complexes seems to be via VB6 transporting membrane carrier med...
Photocytotoxic ternary copper(II) complexes of histamine Schiff base and pyridyl ligands
Journal of Chemical Sciences, 2016
Ternary copper(II) complexes of salicylaldehyde-histamine Schiff base (HL) and pyridyl ligands, viz. [Cu(bpy)(L)](ClO 4) (1) and [Cu(dppz)(L)](ClO 4) (2), where bpy is 2,2-bipyridine (in 1) and dppz is dipyrido[3,2-a:2 ,3-c]phenazine (in 2), were synthesized, characterized and their DNA binding, photo-activated DNA cleavage activity and photocytotoxicity studied. The 1:1 electrolytic one-electron paramagnetic complexes showed a d-d band near 670 nm in aqueous DMF (1:1 v/v). The crystal structure of complex 1 showed the metal in CuN 4 O distorted square-pyramidal geometry. Complex 2 intercalatively binds to calf-thymus (ct) DNA with a binding constant (K b) of ∼10 5 M −1. It exhibited moderate chemical nuclease activity but excellent DNA photocleavage activity in red light of 647 nm forming • OH radicals. It showed remarkable photocytotoxicity in human cervical cancer cells (HeLa) giving IC 50 of 1.6 μM in visible light (400-700 nm) with low dark toxicity. The photo-induced cell death is via generation of oxidative stress by reactive oxygen species.
Dalton Transactions, 2014
of L-amino acid reduced Schiff bases (Fc-aa), 2-(9-anthryl)-1H-imidazo[4,5-f ][1,10]phenanthroline (aip) and 2-(1-pyrenyl)-1H-imidazo[4,5-f ][1,10]phenanthroline ( pyip), where Fc-aa is ferrocenylmethyl-Ltyrosine (Fc-Tyr in 1, 4), ferrocenylmethyl-L-tryptophan (Fc-Trp in 2, 5) and ferrocenylmethyl-L-methionine (Fc-Met in 3, 6), were prepared and characterized, and their photocytotoxicity was studied (Fc = ferrocenyl moiety). Phenyl analogues, viz. [Cu(Ph-Met)(aip)](ClO 4 ) (7) and [Cu(Ph-Met)(pyip)](ClO 4 ) (8), were prepared and used as control compounds. The bis-imidazophenanthroline copper(II) complexes, viz.
A long-lived cuprous bis-phenanthroline complex for the photodynamic therapy of cancer
Dalton transactions (Cambridge, England : 2003), 2018
Copper is an earth-abundant and a biologically essential metal that offers a promising alternative to noble metals in photochemistry and photobiology. In this work, a series of sterically encumbered Cu(i) bis-phenanthroline complexes were investigated for their use in photochemotherapy (PCT). It was found that Cu(dsbtmp)2+ [dsbtmp = 2,9-disec-butyl-3,4,7,8-tetramethyl-1,10-phenanthroline] (compound 3), which possessed the longest excited state lifetime, exhibited significant in vitro photocytotoxicity on A375 (human malignant melanoma) and A549 (human lung carcinoma) cell lines. Fluorescence imaging demonstrated the significant uptake and localization of compound 3 in a perinuclear fashion. A comet assay indicated the induction of DNA damage in the dark. The DNA breaks were significantly amplified upon photoactivation. The light-induced enhancement of cytotoxicity was associated with the formation of reactive oxygen species (ROS), a known intermediate in photodynamic therapy (PDT). ...
Organometallics, 2010
Ferrocene-appended copper(II) complexes [Cu(Fc-tpy)(B)](ClO 4 ) 2 (1-3) and [Cu(Ph-tpy)(dppz)]-(ClO 4 ) 2 (4) as control, where Fc-tpy is 4 0 -ferrocenyl-2,2 0 :6 0 ,2 00 -terpyridine, Ph-tpy is 4 0 -phenyl-2,2 0 :6 0 ,2 00terpyridine, and B is a phenanthroline base, viz., 1,10-phenanthroline (phen, 1), dipyridoquinoxaline (dpq, 2), and dipyridophenazine (dppz, 3), were prepared and structurally characterized, and their DNA binding, photoactivated DNA cleavage activity, and cytotoxic properties were studied [Fc = (η 5 -C 5 H 4 )Fe II (η 5 -C 5 H 5 )]. Complexes 1 and 3 as hexafluorophosphate salts were structurally characterized by X-ray crystallography. Molecular structures of [Cu(Fc-tpy)(phen)](PF 6 ) 2 (1a) and [Cu(Fc-tpy)(dppz)]-(PF 6 ) 2 3 MeCN (3a 3 MeCN) show a distorted square-pyramidal geometry at copper(II), with the Fc-tpy ligand and the phenanthroline base showing respective tridentate and bidentate binding modes. The phenanthroline base exhibits axial-equatorial bonding, while the Fc-tpy ligand binds at the basal plane. The complexes showed quasi-reversible cyclic voltammetric responses near 0.45 and -0.3 V vs SCE in aqueous DMF-0.1 M KCl assignable to the Fc þ -Fc and Cu(II)-Cu(I) redox couples, respectively. The complexes bind to DNA, giving K b values of 1.4 Â 10 4 to 5.6 Â 10 5 M -1 in the order 4 ∼ 3 > 2 > 1. Thermal denaturation and viscometric titration data suggest groove and/or partial intercalative mode of DNA binding of the complexes. The complexes showed chemical nuclease activity in the presence of 3-mercaptopropionic acid (0.5 mM) or H 2 O 2 (0.25 mM). Complexes 2-4 showed plasmid DNA cleavage activity in visible light, forming • OH radicals. The Fc-tpy complex 3 showed better DNA photocleavage activity than its Ph-tpy analogue. The ferrocene moiety in the dppz complex 3 makes it more photocytotoxic than the Ph-tpy analogue 4 in HeLa cells.
Photocytotoxic ferrocene-appended (l-tyrosine)copper(II) complexes of phenanthroline bases
Polyhedron, 2013
a b s t r a c t Copper(II) complexes of ferrocene(Fc)-conjugated reduced Schiff base of L-tyrosine (Fc-TyrH), viz., [Cu(Fc-Tyr)(L)](ClO 4 ), where L is 1,10-phenanthroline (phen, 1), dipyrido[3,2-d:2 0 ,3 0 -f]quinoxaline (dpq, 2), dipyrido[3,2-a:2 0 ,3 0 -c]phenazine (dppz, 3) and 2-(naphthalen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (nip, 4), were prepared and tested for their photocytotoxicity in cancer cells. [Cu(Fc-Phe)(phen)](-ClO 4 ) (5) of L-phenylalanine and [Cu(Ph-Tyr)(L)(ClO 4 )] of the reduced Schiff base Ph-TyrH derived from benzaldehyde and L-tyrosine having phen and dppz , and [Cu(Ph-Phe)(phen)(ClO 4 )] (8) using Lphenylalanine were prepared and used as controls. Complexes 5 and 6 were structurally characterized by X-ray crystallography. A copper(II)-based d-d band near 600 nm and a ferrocenyl band at $450 nm were observed in DMF-Tris-HCl buffer (1:4 v/v) in respective complexes. The complexes are photocleavers of pUC19 DNA in visible light forming OH radicals. They are cytotoxic in HeLa (human cervical cancer) and MCF-7 (human breast cancer) cells showing an enhancement of cytotoxicity in visible light. Fluorescence imaging shows nuclear localization of the complexes.
Journal of Inorganic Biochemistry, 2013
Ternary copper(II) complexes [Cu(NST) 2 (phen)] (1) and [Cu(NST) 2 (NH 3) 2 ]•H 2 O (2) [HNST = N-(4,5dimethylthiazol-2-yl)naphthalene-1-sulfonamide] were prepared and characterized by physico-chemical techniques. Both 1 and 2 were structurally characterized by X-ray crystallography. The crystal structures show the presence of a distorted square planar CuN 4 geometry in which the deprotonated sulfonamide, acting as monodentate ligand, binds to the metal ion through the thiazole N atom. Both complexes present intermolecular π-π stacking interactions between phenanthroline rings (compound 1) and between naphthalene rings (compound 2). The interaction of the complexes with CT DNA was studied by means of thermal denaturation, viscosity measurements and fluorescence spectroscopy. The complexes display good binding propensity to the calf thymus DNA giving the order: 1>2. Complex 1, which has a higher capability for binding to DNA, showed better nuclease activity than 2 in the presence of ascorbate/H 2 O 2. Both the kinetics and the mechanism of the DNA cleavage reaction were investigated. Furthermore, complex 1 showed efficient photo-induced DNA cleavage activity on irradiation with UV light in the absence of any external reagent. The UV light induced DNA cleavage follows a photo-redox pathway with generation of hydroxyl radicals as reactive species. In addition, the cytotoxic properties of both complexes (1 and 2) were evaluated in human cancer cells (HeLa, Caco-2 and MDA-468). The low IC 50 values, in particular those against Caco-2, have indicated that the compounds can be considered as promising chemotherapeutic agents.
Copper(II) complexes [Cu(satp)(L)] (1–3) of a Schiff base thiolate (salicylidene-2-aminothiophenol, H2satp) and phenanthroline bases (L), viz. 1,10-phenanthroline (phen in 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq in 2) and dipyrido[3,2-a:2′,3′-c]phenazine (dppz in 3), were prepared, characterized and their anaerobic DNA photocleavage activity and hypoxic photocytotoxicity studied. The redox active complexes show the Cu(II)–Cu(I) couple near − 0.5 V for 1 and near 0.0 V vs. SCE (saturated calomel electrode) for 2 and 3. The one-electron paramagnetic complexes (~ 1.85 μB) are avid DNA binders giving Kb values within 1.0 × 105 − 8.0 × 105 M− 1. Thermal melting and viscosity data along with molecular docking calculations suggest DNA groove and/or partial intercalative binding of the complexes. The complexes show anaerobic DNA cleavage activity in red light under argon via type-I pathway, while DNA photocleavage in air proceeds via hydroxyl radical pathway. The DFT (density functional theory) calculations reveal a thyil radical pathway for the anaerobic DNA photocleavage activity and suggest the possibility of generation of a transient copper(I) species due to bond breakage between the copper and sulfur to generate the thyil radical. An oxidation of the copper(I) species is likely by oxygen in an aerobic medium or by the buffer medium in an anaerobic condition. Complex 3 exhibits significant photocytotoxicity in HeLa cells (IC50 = 8.3(± 1.0) μM) in visible light, while showing lower dark toxicity (IC50 = 17.2(± 1.0) μM). A significant reduction in the dark toxicity is observed under hypoxic cellular conditions (IC50 = 30.0(± 1.0) μM in dark), while retaining its photocytotoxicity (IC50 = 8.0(± 1.0) μM).
Research Square (Research Square), 2024
Chemotherapy plays a role in many cancer therapies, including breast cancer, but due to its signi cant side effects, alternate treatment approaches have been investigated. One such alternative is Photodynamic Therapy (PDT), which employs a combination of oxygen, a photosensitizer (PS), and light of a speci c wavelength. Transition metal complexes and SBL have gained interest in PDT. In this study aimed to assess the potential antitumor activity and underlying mechanism of a newly synthesized Schiff Base Ligand (SBL)-mediated PDT on MCF-7 cells, comparing its e cacy to cisplatin. We synthesized and characterized two novel Pd-conjugated SBL compounds (complex-1 and 2). Following the treatment of MCF-7 cells with these compounds, a Light-Emitting Diode (LED) was utilized to deliver a light dose of 14.8 J/cm 2. In MCF-7 cells, we also looked at cytotoxicity, cell death rates, and ROS levels. Results indicated a signi cant increase in cytotoxicity and ROS levels in the group treated with complex-1 mediated PDT. The apoptotic and necrotic cell death also rose signi cantly. In conclusion, our study suggests that the complex-1 compound may serve as a promising candidate for anticancer agents in PDT for MCF-7 cells. In contrast, complex-2 mediated PDT did not demonstrate any observable anticancer activity.