Intrinsic resistance of cancer cells is a major concern for the success of chemotherapy, and this undesirable feature stimulates further research into the design of new compounds and/or alternative ...multiple drug chemotherapy protocols.
In this study, we investigated the antitumoral potential of the coordination compounds Cu(HPClNOL)ClCl (1), Fe(HPClNOL)Cl2NO3(2) and Mn(HPClNOL)Cl2 (3). Using the human, MCF-7 and A549, and the murine melanoma, B16-F10, cell lines, we determined the cytotoxicity, DCFH oxidation, disruption of mitochondrial membrane potential (ΔΨm), Sub-G1 and TUNEL positive cells, and caspase 8 and 9 activities. Fractional inhibitory concentration (FIC) and xenograft models were also assessed to evaluate the efficacy of antitumoral potential.
We observed that only complex 1 was cytotoxic. The treatment of cancer cells with complex 1 triggered ROS generation and promoted the disruption of ΔΨm. Complex 1 increased the number of Sub-G1 and TUNEL positive cells, and the measurement of caspase 8 and 9 activity confirmed that apoptosis was triggered by the intrinsic pathway. FIC demonstrated that the combination of complex 1 with cisplatin was additive for the A549 cells whilst it was synergic for MCF-7 and B16-F10. Treatment with complex 1, either alone or combined with cisplatin, reduced tumor growth on xenograft models.
The present study brings new clues regarding the mechanism of action of Cu(HPClNOL)ClCl, either alone or in combination with cisplatin.
These results indicate that complex 1, administered either singly or in combination with current drugs, has real potential for use in cancer therapy.
Crystal structure of the synthesized copper(II) complex with 6-methylpyridine-2-carboxylic acid, Cu(6-Mepic)2·H2O·H2O, was determined by XRD, FT-IR and UV–Vis spectroscopic techniques. Furthermore, ...the geometry optimization, harmonic vibration frequencies for the Cu(II) complex were carried out by using Density Functional Theory calculations with HSEh1PBE/6-311G(d,p)/LanL2DZ level. Electronic absorption wavelengths were obtained by using TD-DFT/HSEh1PBE/6-311G(d,p)/LanL2DZ level with CPCM model and major contributions were determined via Swizard/Chemissian program. Additionally, the refractive index, linear optical (LO) and non-nonlinear optical (NLO) parameters of the Cu(II) complex were calculated at HSEh1PBE/6-311G(d,p) level. The experimental and computed small energy gap shows the charge transfer in the Cu(II) complex. Finally, the hyperconjugative interactions and intramolecular charge transfer (ICT) were studied by performing of natural bond orbital (NBO) analysis.
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•The growth Cu(II-6-Mepic crystal was obtained.•Optical band gap was obtained by UV–Vis spectrum.•The NLO parameters (β, γ and χ(3)) were investigated.•TD/DFT calculations were performed to support experimental results.
•The Copper-Schiff base@MCM-41 was successfully synthesized using the ultrasonication method, resulting in a material with expected morphological and structural features.•Various characterization ...techniques including UV-DRS, FTIR, LXRD, SEM, EDAX, ICP-AES, HR-TEM, BET, TGA-DTA, and ESR analyses were employed to confirm the formation of the desired material and investigate its properties.•The Copper-Schiff base@MCM-41 catalyst exhibited excellent catalytic activity in the Biginelli reaction under an eco-friendly solvent approach at room temperature. The reaction achieved a high product yield, indicating the effectiveness of the catalyst.•After the completion of the reaction, the Copper-Schiff base@MCM-41 catalyst was easily recovered using the filtration method and could be reused for another reaction.•The Copper-Schiff base@MCM-41 catalyst demonstrated superior performance as a heterogeneous catalyst for the Biginelli reaction compared to other catalysts. Its excellent catalytic activity, achieving high product yield in a short time at room temperature, showcased its effectiveness and potential in catalytic applications. A plausible reaction mechanism was also proposed based on the study, contributing to the understanding of the catalytic process.
A Copper(II) Schiff-base complex immobilized mesoporous silica-41 (Copper-Schiff base@MCM-41) was synthesized using the ultrasonication method. The formation of material with expected morphological and structural features was confirmed with various characterization techniques including UV-DRS, FTIR, LXRD, SEM, EDAX, ICP-AES, HR-TEM, BET, TGA-DTA, and ESR analyses. Furthermore, the Copper-Schiff base@MCM-41 catalyzed Biginelli reaction has performed under an eco-friendly solvent approach at room temperature, achieving high product yield. After the completion of the reaction, the catalyst was easily recovered using the filtration method and reused for another reaction, maintaining comparable product yield up to five repetitive cycles without any major catalytic activity decay. The exhibition of excellent catalytic activity towards 3,4-dihydropyrimidone derivatives with high product yield in a short time at room temperature proved that the Copper-Schiff base@MCM-41 is a more effective heterogeneous catalyst toward the Biginelli reaction compared to other catalysts. The plausible reaction mechanism has proposed based on the study.
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•The new analytical copper(II) based ara-C analog (an anticancer drug) was synthesized according to different analytical conditions and characterized by analytical and spectroscopic methods.•All ...chemical activity analyses of the molecules were performed on the basis of by DFT method B3LYP functional and LANL2DZ (Cu(II) atom), 6-311G(d,p) mixed basis sets (carbon, oxygen, nitrogen, chlorine and hydrogen atoms).•The interactions between the molecule with DNA bases such as adenine, cytosine, guanine, and thymine were investigated by using the ECT (electrophilicity-based charge transfer) method for ara-C and Cu2(ara-C)2Cl4.•Molecular docking and DNA binding analysis were performed for ara-C and Cu2(ara-C)2Cl4.•The hyperconjugation interaction energy and electron densities of donor and acceptor bonds were calculated by using natural bond orbital (NBO) analysis for Cu2(ara-C)2Cl4.
In this study, the new copper(II) based cytosine arabinoside (ara-C) analog was synthesized and characterized by analytical and spectroscopic methods. Especially the data obtained from FT-IR spectroscopy showed that ara-C coordinated with copper(II) ions through –C=O and -Nring groups and formed a complex compound in a tetrahedral structure. The proposed structure of this dimeric copper(II) complex was defined as Cu2(ara-C)2Cl4. Also, the ability of both compounds to bind to double helix fish sperm DNA (dsDNA) and the damage to the HeLa cell line was investigated. All theoretical chemical activity analyses (hardness and softness parameters, Fukui functions, net charges) of the ara-C and Cu2(ara-C)2Cl4 molecules were performed with DFT with mixed basis set including LANL2DZ for Cu atom and 6-311G(d,p) for carbon, oxygen, nitrogen, chlorine and hydrogen atoms with B3LYP functional was applied. The stability of the molecule arising from hyperconjugative interactions, charge delocalization was analyzed by using natural bond orbital analysis (NBO) for optimized structure of Cu2(ara-C)2Cl4. Also, the interactions between the studied molecules (ara-C and Cu2(ara-C)2Cl4 with DNA bases such as adenine, cytosine, guanine, and thymine were investigated by using the ECT (electrophilicity-based charge transfer) method. Furthermore, the best binding sites of the DNA (PDB:1BNA) protein to the ligands (ara-C and Cu2(ara-C)2Cl4 were examined and the binding energies and interaction states were determined by molecular docking study.
Copper complexes of patellamides have shown catalytic activity in a variety of reactions but their biological function remains unknown. There are significant differences between the natural ...macrocycles and synthetic analogues in the various catalytic activities. It therefore is essential to be able to perform in vivo and ex vivo reference measurements with the natural patellamide macrocycles, very similar derivatives and a large range of synthetic analogues. The preparative method described allows for a highly adaptable synthetic process producing building blocks for a large range of patellamide derivatives: apart from natural compounds, a new synthetic patellamide was prepared that does not have any substituents at any of the four heterocycles. Together with the variation of substituents at the aliphatic backbone, this allowed to elucidate the catalytic activity for phosphoester hydrolysis as a function of the structure and dynamics of the dicopper(II)‐patellamide complexes, both by experiment and DFT‐based mechanistic studies.
An efficient synthetic procedure for natural and artificial patellamides, found in the ascidians of the Great Barrier Reef, is presented. These macrocycles are known to tightly bind CuII, and the variety of easily available patellamide derivatives allows to carefully study the reactivity as a function of the structure of the macrocycle. This has been done by experiment and DFT for phosphatase activity as a possible reaction of metabolic relevance.
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•Coumarin Thiosemicarbazones: acidic hydrogen at N(1) involved in intramolecular hydrogen bonding with lactone carbonyl forming more stable E isomer than Z isomer.•Cu(II) complex: ...distorted square planar, carbonyl O, imine N, thiolate S−, and Cl− ion coordinated.•In Vitro: anticancer activity in dose dependent manner against MCF-7 and MDA-MB-231 cells.•In Silico: follows Lipinski’s rule and high binding energy (−5.8 to −8.0 Kcal/mol) against EGFR and HER-2.
A series of 3-acetylcoumarin-based thiosemicarbazones and their copper(II) complexes were synthesized and characterized by elemental analysis, IR, UV–Vis, HR-ESI Mass, NMR, EPR and single crystal XRD. The XRD study revealed thione tautomer for TSCs 3 (AcCmDEtTSC) and 4 (AcCmDPrTSC) whereas Cu(II) complex 8Cu(AcCmDPrTSC)Cl has distorted square planar geometry around the metal ion. Compound 1 (AcCmMeHTSC) among the thiosemicarbazones (TSCs) was more effective against both breast cancer cell lines: MCF-7 (IC50; 13.02 µg/mL) and MDA-MB-231 (IC50; 42.71 µg/mL), whereas compounds 7Cu(AcCmDEtTSC)Cl (IC50; 32.84 µg/mL) and 8Cu(AcCmDPrTSC)Cl (IC50: 34.69 µg/mL) among the Cu(II) complexes were more effective against MDA-MB-231 cell lines. Anticancer activity of the test compounds enhanced in dose dose-dependent manner against both MCF-7 and MDA-MB-231 cells. Molecular docking study showed significant binding affinity of the test compounds, notably compound 2 (AcCmEtHTSC) with −7.1 kcal/mol and −8.0 kcal/mol, compound 3 with −7.3 kcal/mol and −7.8 kcal/mol against target proteins EGFR and HER2 respectively. Although the IC50 value of the synthesized compounds is not very encouraging, their significant binding affinity values (−5.8 kcal/mol to −8.0 kcal/mol) against the target proteins EGFR and HER 2 is encouraging for the further exploration of their anticancer activity in the future.
Herein we report on the synthesis and characterization of new water-soluble complexes with the basic formula Cu(ON)(NN)(ClO4)2, where ON = 4-aminoantipyrine and NN = 1,10-phenanthroline (1) or ...2,2ʹ-bipyridine (2). Both complexes have distorted tetragonal geometry around each copper centre, which is coordinated to both bidentate ligands in equatorial sites with two perchlorate ions weakly bonded in the axial positions. The compounds bind to DNA and induce oxidative DNA damage mediated by reactive oxygen species (ROS). Both complexes inhibit the growth of K562 cells in a concentration-dependent manner with IC50 values lower than the corresponding free ligands. Significantly, the most cytotoxic agent (complex 1) presented high in vitro nucleolytic activity by generating single- and double-strand breaks, besides of inhibiting topoisomerase I enzymatic activity at low micromolar concentration.
We report two new Cu(II) complexes with 4-aminoantipyrine able to prevent topoisomerase I activity, induce DNA cleavage and inhibit the growth of cancer cells. Display omitted
•Water-soluble Cu2+ complexes able to bind to DNA and induce oxidative DNA damage.•Inhibition of the growth of tumor cells (K562 cell line), IC50 = 1.8 μM.•Inhibition of topoisomerase I enzymatic activity at 5.0 μM.
•Reaction of 1,3-bis(4-chloro)benzenetriazene (HL) and CuCl2·2H2O affords a complex, Cu2L4(NCCH3) 1.•Structure of 1 is determined by single crystal X-ray diffraction analysis.•Complex 1 is capable of ...generating hydrogen from acetic acid or water.•TOF reaches a maximum of 43 (DMF) and 198 (buffer, pH 6) moles/mole/h, respectively.
The reaction of 1,3-bis(4-chloro)benzenetriazene (HL) and CuCl2·2H2O affords a dinuclear triazenido–copper(II) complex Cu2L4(NCCH3) (1), a new molecular electrocatalyst, which has been determined by X-ray crystallography. Electrochemical studies show that complex 1 can catalyze hydrogen evolution from acetic acid or water. Turnover frequency (TOF) reaches a maximum of 43 (in DMF) and 174 (in phosphate buffer, pH 6) moles of hydrogen per mole of catalyst per hour, respectively. Sustained proton reduction catalysis occurs at glassy carbon (GC) electrode to give H2 over a 72h electrolysis period and no observable decomposition of the catalyst.
Three novel hybrid inorganic-organic copper(II) 2,4,5-trichlorophenoxyacetate complexes Cu(γ-pic)3(L)2·H2O 1, trans-Cu(en)2(L)2·2H2O 2 and Cu2(H2tea)2(L)2·2H2O 3 have been synthesized and ...characterized by elemental analyses, TGA, spectroscopic techniques (IR, UV/VIS and EPR), conductance measurements, magnetic susceptibility studies and single crystal X-ray structure determination. The crystal lattice is stabilized by framework of supramolecular interactions.
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•Three novel hybrid copper(II) 2,4,5-trichlorophenoxyacetate complexes were synthesized.•Crystal lattice is stabilized by array of non-covalent interactions.•All complexes show similar mode of carboxylate coordination (monodentate).•Variety of structural frameworks in presence of different ligands.•Complex 2 shows dual nature (ionic in solution state and covalent in solid state).
Three novel coordination complexes of copper(II) with 2,4,5-trichlorophenoxyacetate Cu(γ-pic)3(L)2·H2O 1, trans-Cu(en)2(L)2·2H2O 2 and Cu2(H2tea)2(L)2·2H2O 3, where L=2,4,5-trichlorophenoxyacetate, γ-pic=γ-picoline, en=ethylenediamine, H2tea=monodeprotonated triethanolamine, were synthesized by addition of γ-picoline/ethylenediamine/triethanolamine, respectively, to the hydrated Cu(2,4,5-trichlorophenoxyacetate)2 suspended in methanol-water (4:1, v/v). The newly synthesized complexes have been characterized by elemental analyses, spectroscopic techniques (UV–Vis and FT-IR), magnetic moment determination, molar conductance studies, TGA and single crystal X-ray diffraction method. The structure determination revealed neutral nature of complexes in all the three cases, with different coordination geometry around the copper(II) metal centre depending upon nature of the N- or N,O-donor ligands. Hydrogen bonding network i.e. O–H⋯O and C–H⋯O in complexes 1, 3 and N–H⋯O, and O–H⋯O in complex 2 stabilizes crystal lattice in copper(II) complexes besides other non-covalent interactions.
In this manuscript, a new colorimetric and fluorescent chemosensor (T) was designed and synthesized, it could successively detect Cu2+ and H2PO4− in DMSO/H2O (v/v=9:1, pH=7.2) buffer solution with ...high selectivity and sensitivity. When added Cu2+ ions into the solution of T, it showed a color changes from yellow to colorless, meanwhile, the green fluorescence of sensor T quenched. This recognition behavior was not affected in the presence of other cations, including Hg2+, Ag+, Ca2+, Co2+, Ni2+, Cd2+, Pb2+, Zn2+, Cr3+, and Mg2+ ions. More interestingly, the Cu2+ ions contain sensor T solution could recover the color and fluorescence upon the addition of H2PO4− anions in the same medium. And other surveyed anions (including F−, Cl−, Br−, I−, AcO−, HSO4−, ClO4−, CN− and SCN−) had nearly no influence on the recognition behavior. The detection limits of T to Cu2+ and T-Cu2+ to H2PO4− were evaluated to be 1.609×10−8M and 0.994×10−7M, respectively. In addition, the sensor T also could be served as a recyclable component and the logic gate output was also defined in sensing materials. The test strips based on sensor T were fabricated, which acted as a convenient and efficient Cu2+ and H2PO4− test kits.
A specially selectivity and highly sensitivity ON-OFF-ON reversible chemosensor T based on imine bound as the recognize side and N,N-diethyl as the fluorescence signal report group had been designed and synthesized. Display omitted
•A highly selective and sensitive reversible fluorescent sensor for detecting Cu2+ and H2PO4− in aqueous media.•The change of recognition process can be detected by naked eyes.•The test strips could conveniently detect Cu2+ and H2PO4− in aqueous media.
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