DNA binding, nuclease activity, DNA photocleavage and cytotoxic properties of Cu(II) complexes of N-substituted sulfonamides (original) (raw)
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Polyhedron, 2009
Ternary copper(II) complexes (1-3) of 1,10-phenanthroline and ethylenediamine-R-sulfonamide derivatives (R = benzene, toluene and naphthalene rings) have been synthesized and characterized with the aid of X-ray diffraction and spectroscopic and electrochemical techniques. The crystal structures of the complexes show that the coordination polyhedron around copper(II) is distorted square planar. Both 1,10phenanthroline and ethylenediamine-R-sulfonamide act as bidentate ligands. The three structures are stabilized by p-p stacking interactions. The interaction of the complexes with calf thymus DNA has been investigated by thermal denaturation studies which indicated that DNA was stabilized in the presence of the compounds. The increase in DNA stability induced by the complexes follows the order: 3 > 2 > 1. All three complexes were found to be very efficient agents of plasmid DNA cleavage in the presence of ascorbate as reducing agent. Mechanistic studies of the DNA cleavage process performed with radical scavengers show that the reactive oxygen species involved in the DNA damage are the hydroxyl radical, singlet oxygen-like species, the superoxide * and hydrogen peroxide.
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...
DNA binding, nuclease activity and cytotoxicity studies of Cu(ii) complexes of tridentate ligands
Dalton Transactions, 2012
ethanamine] respectively, were synthesized and characterized. The single crystal X-ray structure of complex 1 reveals the pseudo octahedral coordination geometry around the copper center. Absorption and fluorescence experimental evidence show good DNA binding propensity (in the order of 10 5 M −1 ) of the complexes. Thermal denaturation and circular dichroism (CD) analyses reveal minor structural changes of calf thymus (CT) DNA in presence of complexes and groove and/or surface binding of the complexes to CT-DNA. Kinetic DNA cleavage assay shows pseudo-first-order kinetic reaction between the complex and supercoiled (SC) DNA. In addition, mechanistic SC DNA cleavage results show higher DNA cleavage activity in presence of reducing agent, due to the presence of hydroxyl radicals. In vitro cytotoxicity assay of the complexes demonstrate that the complexes have low toxicity for different cancer cell lines and IC 50 values were between 37 and 156 μM. Fig. 1 Ligands used for the present study. † Electronic supplementary information (ESI) available. CCDC reference number 865490. For ESI and crystallographic data in CIF or other electronic format see Scheme 2 Synthesis of complex 1. 7576 | Dalton Trans., 2012, 41, 7573-7581 This journal is
Journal of Inorganic Biochemistry, 2014
A series of mononuclear mixed ligand copper(II) complexes of the type [Cu(L)(2,9-dmp)](ClO 4 ) 2 1-4, where L is a tridentate 3N ligand such as diethylenetriamine (L1) (1)orN-methyl-N′-(pyrid-2-yl-methyl)ethylenediamine (L2) (2) or di(2-picolyl)amine (L3) (3) or bis(pyrid-2-ylmethyl)-N-methylamine (L4) (4) and 2,9-dmp is 2,9dimethyl-1,10-phenanthroline, has been isolated and characterized. The complexes 1 and 3 possess squarebased pyramidal coordination geometry. Absorption spectral studies reveal that the intrinsic DNA binding affinity varies as 1 N 2 N 3 N 4. The higher DNA binding affinity of 1 arises from L1, which offers lower steric hindrance toward intercalation of 2,9-dmp co-ligand into DNA base pairs and is involved in hydrogen bonding interaction with DNA. Interestingly, all the complexes cleave pUC19 supercoiled DNA in the absence of an activating agent. They also exhibit oxidative (H 2 O 2 ) DNA cleavage ability, which varies as 1 N 2 N 3 N 4, the highest cleavage efficiency of 1 being due to the largest amount of ROS it generates. The tryptophan emission-quenching experiment reveals that the stronger binding of 3 and 4 with bovine serum albumin (BSA) in the hydrophobic region, which is in line with DNA viscosity measurements. The IC 50 values of 1-4 for MCF-7 breast cancer cell line are lower than that of cisplatin. Flow cytometry analysis reveals that 1 mediates the arrest of S and G2/M phases in the cell cycle progression at 24 h harvesting time, which progresses into apoptosis. Hoechst 33258 staining studies indicate the higher potency of 1 to induce apoptosis.
Inorganic Chemistry, 2011
Two mononuclear fluorophore-labeled copper(II) complexes [Cu(nip)(acac)] þ (2) and [Cu(nip) 2 ] 2þ (3), where fluorophore is 2-(naphthalen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (nip) (1) and acac is acetylacetone, have been synthesized and characterized by various techniques. The ligand 1 and complex 2 are structurally characterized by single-crystal X-ray diffraction. The coordination geometries around the copper are square planar in solid as well as solution state as evidenced by electron paramagnetic resonance (EPR) spectroscopy. The density functional calculations carried out on 1-3 have shown that electron-rich regions in the highest occupied orbital are localized on the naphthalene and partly on the phenanthroline moiety. Both complexes 2 and 3 in dimethyl sulfoxide (DMSO) exhibit near square planar structure around the metal ion in their ground state. Time-dependent density functional theory (TD-DFT) calculations reveal that Cu(II) ion in complex 2 shows tetrahedral coordination around the metal while 3 retains its square planar geometry in the lowest excited state. The interaction of complexes with calf-thymus DNA (CT DNA) has been explored by using absorption, emission, thermal denaturation, and viscosity studies, and the intercalating mode of DNA binding has been proposed. The complexes cleave DNA oxidatively without any exogenous additives. The protein binding ability has been monitored by quenching of tryptophan emission in the presence of complexes using bovine serum albumin (BSA) as model protein. The compounds showed dynamic quenching behavior. Further, the anticancer activity of the complexes on MCF-7 (human breast cancer), HeLa (human cervical cancer), HL-60 (human promyelocytic leukemia), and MCF-12A (normal epithelial) cell lines has been studied. It has been observed that 3 exhibits higher cytotoxicity than 2, and the cells undergo apoptotic cell death.
Photoactivated cytotoxicity of ferrocenyl-terpyridine oxovanadium(IV) complexes of curcuminoids
European journal of medicinal chemistry, 2014
Oxovanadium(IV) complexes, viz. [VO(Fc-tpy)(Curc)](ClO4) (1), [VO(Fc-tpy)(bDHC)](ClO4) (2), [VO(Fc-tpy)(bDMC)](ClO4) (3) and [VO(Ph-tpy)(Curc)](ClO4) (4), of 4'-ferrocenyl-2,2':6',2″-terpyridine (Fc-tpy) and 4'-phenyl-2,2':6',2″-terpyridine (Ph-tpy) and monoanionic curcumin (Curc), bis-dehydroxycurcmin (bDHC) and bis-demethoxycurcumin (bDMC) were prepared, characterized and their photo-induced DNA cleavage activity and photocytotoxicity in visible light studied. The ferrocenyl complexes 1-3 showed an intense metal-to-ligand charge transfer band near 585 nm in DMF and displayed Fc(+)/Fc and V(IV)/V(III) redox couples near 0.65 V and -1.05 V vs. SCE in DMF-0.1 M TBAP. The complexes as avid binders to calf thymus DNA showed significant photocleavage of plasmid DNA in red light of 647 nm forming OH radicals. The complexes showed photocytotoxicity in HeLa and Hep G2 cancer cells in visible light of 400-700 nm with low dark toxicity. ICP-MS and fluorescence microsc...
Inorganic Chemistry, 2007
The copper(II) complex [Cu(tdp)(ClO 4 )]‚0.5H 2 O (1), where H(tdp) is the tetradentate ligand 2-[(2-(2-hydroxyethylamino)ethylimino)methyl]phenol, and the mixed ligand complexes [Cu(tdp)(diimine)] + (2−5), where diimine is 2,2′-bipyridine (bpy) (2), 1,10-phenanthroline (phen) (3), 3,4,7,8-tetramethyl-1,10-phenanthroline (tmp) (4), and dipyrido-[3,2-d: 2′,3′-f]-quinoxaline (dpq) (5), have been isolated and characterized by analytical and spectral methods. Complexes 1 and [Cu(tdp)(phen)]ClO 4 (3) have been structurally characterized, and their coordination geometries around copper-(II) are described as distorted octahedral. The equatorially coordinated ethanolic oxygen in 1 is displaced to an axial position upon incorporating the strongly chelating phen, as in 3. The solution structures of all the complexes have been assessed to be square-based using electronic absorption and electron paramagnetic resonance (EPR) spectroscopy. The interaction of the complexes with calf thymus DNA (CT DNA) has been explored by using absorption, emission, and circular dichroic spectral and viscometric studies, and modes of DNA binding for the complexes have been proposed. Absorption spectral (K b ) 0.071 ± 0.005 (2), 0.90 ± 0.03 (3), 7.0 ± 0.2 (4), 9.0 ± 0.1 × 10 5 M -1 (5)), emission spectral (K app ) 4.6 (1), 7.8 (2), 10.0 (3), 12.5 (4), 25.0 × 10 5 M -1 (5)), and viscosity measurements reveal that 5 interacts with DNA more strongly than the other complexes through partial intercalation of the extended planar ring of the coordinated dpq with the DNA base stack. Interestingly, only complex 4 causes a B to A conformational change upon binding DNA. All the complexes hydrolytically cleave pBR322 supercoiled DNA in 10% DMF/5 mM Tris-HCl/50 mM NaCl buffer at pH 7.1 in the absence of an activating agent, and the cleavage efficiency varies in the order 5 > 3 > 2 > 4 > 1 with 5 displaying the highest K cat value (5.47 ± 0.10 h -1 ). The same order of cleavage is observed for the oxidative cleavage of DNA in the presence of ascorbic acid as a reducing agent. Interestingly, of all the complexes, only 5 displays efficient photonuclease activity through double-strand DNA breaks upon irradiation with 365 nm light through a mechanistic pathway involving hydroxyl radicals. The protein binding ability of 1−5 has been also monitored by using the plasma protein bovine serum albumin (BSA), and 4 exhibits a protein binding higher than that of the other complexes. Further, the anticancer activity of the complexes on human cervical epidermoid carcinoma cell line (ME180) has been examined. Interestingly, the observed IC 50 values reveal that complex 4, which effects conformational change on DNA and binds to BSA more strongly, exhibits a cytotoxicity higher than the other complexes. It also exhibits approximately 100 and 6 times more potency than cisplatin and mitomycin C for 24 and 48 h incubation times, respectively, suggesting that 4 can be explored further as a potential anticancer drug. Complexes 4 and 5 mediate the arrest of S and G 2 /M phases in the cell cycle progression at 24 h harvesting time, which progress into apoptosis.
Journal of the Iranian Chemical Society, 2012
A water-soluble Cu (II) complex [(dien)Cu (l-1,6-DAH)Cu(dien) (NO 3) 2 ](NO 3) 2 has been synthesized and its effect on the carrier model DNA structure and cancer cell line proliferation was investigated. In this regard, calf thymus DNA (CT-DNA) and human breast cancer cell line, T47D, were the targets. The effect of the complex on DNA structure was investigated by means of UV/vis, fluorescence and circular dichroism (CD) spectroscopic techniques as well as dynamic light scattering (DLS), zeta potential analysis and docking assay for more analysis. The UV-vis absorption spectra of complex with DNA showed a slight red shift and hypochromic effect, which indicated the intercalation and electrostatic effect of complex with CT-DNA. Using ethidium bromide (EB) as a probe in fluorescence studies revealed that complex can quench the EB-DNA fluorescence emission at different temperatures. Besides, the far UV-CD studies displayed that the complex induces changes in the secondary structure of CT-DNA and can increase the melting temperature of DNA up to 14°C. The DLS and zeta potential measurements confirmed the electrostatic interaction of complex with the negatively charged DNA and subsequent DNA condensation. Besides, computational studies reflect that major and minor groove binding are two modes of interaction between complex and DNA. On the other hand, growth inhibition of the complex toward T47D cell line was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, which showed no cytotoxic properties.
Vitamin-B6 (VB6) Schiff base (H 2 L) 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 dipyrido[3,2-a:2,3c]phenazine are synthesized, characterized and their phto-induced anticancer activity studied. The non-electrolytic oneelectron 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 ~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 radical. It displays remarkable photocytotoxicity in human cervical cancer cells (HeLa) giving IC 50 value of 0.9 M in visible light (400-700 nm) while being less toxic in darkness (IC 50 : 23 M). The cellular uptake of the complexes seems to be via VB6 transporting membrane carrier mediated diffusion pathway. Photo-induced cell death follows apoptotic pathway involving photo-generated intracellular reactive oxygen species.