Synthesis and biological evaluation of Cu(II), Zn(II), and Ni(II) 3-(4-nitrophenyl)acrylic acid complexes with diamines as potential urease inhibitors

Five new Cu(II), Zn(II), and Ni(II) 3-(4-nitrophenyl)acrylic acid complexes were synthesized and evaluated for inhibitory activity on jack bean urease. All five complexes were structurally determined by single crystal X-ray analysis. Compared with the positive reference acetohydroxamic acid (IC₅₀?=?13.25?μM), Cu(II) complexes 3 and 4 showed the strongest inhibitory activity against jack bean urease (IC₅₀?=?1.23 and 1.17?μM). Ni(II) and Zn(II) complexes also exhibited inhibitory activities (IC₅₀?=?10.09–13.10?μM).     

Synthesis,urease inhibitory activities,and molecular docking studies of two Cu(II) complexes

Two mononuclear copper(II) complexes, [Cu(C₄H₃N₂O₂)₂?·?4H₂O] (1) and [Cu(C₁₂H₁₁N₂O₂Cl₂)₂] (2), were synthesized and structurally characterized by single-crystal X-ray analysis. The copper(II) adopts a square-planar environment in 1, while the geometry in 2 can be described as distorted square-pyramidal. Complexes 1 and 2 were evaluated for their inhibitory activities against jack bean urease in vitro and both were found to have strong inhibitory activities comparable to that of acetohydroxamic acid. A docking simulation was performed to position 2 into the jack bean urease active site to determine the probable binding conformation.     

Synthesis,solid-state structures,and urease inhibition activities of new copper(II) complexes based on O,N,O-tridentate Schiff bases

Six new complexes of copper(II) coordinated with O,N,O-tridentate Schiff base dianions were synthesized and structurally characterized. The solid-state structures of 1–6 contain four-coordinate mononuclear copper(II) units with a slightly distorted square planar geometry. Complexes 1 and 4 derived from d-tyrosine have an infinite 1-D, right-handed helical chain, while 5 derived from l-tyrosine has an infinite 1-D, left-handed helical chain. Inhibitions of jack bean urease by 1–6 have been investigated, and potent inhibitory activities with IC₅₀ range of 2.15 ± 0.11–32.12 ± 0.65 μM have been observed for these copper(II) complexes. A docking analysis using a DOCK program was conducted to position 4 into the jack bean urease active site to determine the probable binding conformation.     

Synthesis,crystal structure,and urease inhibition studies of copper(II) and cobalt(III) complexes with bi(2-fluorobenzylaminoethyl)amine

Three new mononuclear Cu(II) and Co(III) complexes [Cu(L)Cl]ClO₄ (1), [Cu(L)Cl(SCN)] (2), and [Co(L)(N₃)₃] (3), where L is a reduced Schiff-base ligand bi(2-fluorobenzylaminoethyl)amine, were synthesized and characterized. X-ray crystallographical analysis reveals that the Cu(II) atom adopts a square-planar environment in complex 1, while the geometry in 2 can be described as distorted square-pyramidal. The Co(III) atom in 3 is in a distorted octahedral geometry. Three complexes were investigated for their inhibitory activities in vitro against jack bean urease. The Cu(II) complexes 1 and 2 were found to have excellent inhibitory activities. The Co(III) complex 3 was also shown to have activity comparable to that of acetohydroxamic acid.     

Preparation and structural characterization of oxovanadium(V) complexes with Schiff bases and their inhibition studies on Helicobacter pylori urease

A series of structurally similar dinuclear oxovanadium(V) complexes, [VO₂L]₂ (L?=?L¹?=?2-[(2-methylaminoethylimino)methyl]phenolate (1); L?=?L²?=?2-[(2-ethylaminoethylimino)methyl]phenolate (2); L?=?L³?=?2-[(2-isopropylaminoethylimino)methyl]phenolate (3)), has been synthesized and characterized by physico-chemical methods and single-crystal X-ray diffraction. The V in each complex is octahedral, with three donors of L and one oxo defining the equatorial plane, and with two oxos occupying the axial positions. The complexes were tested for their urease inhibitory activities. The inhibition rate (%) of 1, 2, and 3 at 100?µmol?L^?1 on urease are 67?±?1, 53.5?±?0.9, and 44?±?1. The relationship between structures of the complexes and the urease inhibitory activities indicates that shorter terminal groups of the complexes have stronger activities against urease. Molecular docking study of the complexes with the Helicobacter pylori urease was performed.     

Binuclear copper(II) complexes of 1-amidino-O-alkylurea (alkyl = n-propyl,n-butyl,or i-butyl) and vanadate: an EPR study

Five new complexes of bis(1-amidino-O-alkylurea)Cu(II)vanadate where alkyl?=?methyl, ethyl, n-propyl, n-butyl or i-butyl have been synthesized by reaction of ammonium metavanadate with bis(1-amidino-O-alkylurea)Cu(II)perchlorate complexes. Electron paramagnetic resonance (EPR) spectra of bis(1-amidino-O-n-propylurea)Cu(II)vanadate (1), bis(1-amidino-O-n-butylurea)Cu(II)vanadate (2) and bis(1-amidino-O-i-butylurea)Cu(II)vanadate (3) gave half-field signal (ΔM _s?=?±2) ca 1623G, in addition to fine structure due to zero field splitting (ZFS) characteristics of the S?=?1 system. From the observed ZFS the average Cu–Cu distance was estimated. The isotropic exchange constant J was evaluated by recording EPR spectra at different temperatures. The photoacoustic signal of the complexes indicated square-planar geometry around Cu²⁺. X-ray powder diffraction studies on 2 suggested orthorhombic structure with unit cell dimensions a?=?21.11?Å, b?=?24.11?Å, c?=?27.11?Å, α?=?β?=?γ?=?90°. The crystal structure of bis(1-amidino-O-n-butylurea)Cu(II)perchlorate is also reported.     

Dinuclear copper(II) complexes of Fenoprofen: synthesis,spectroscopic, thermal,and SOD-mimic activity studies

Three dinuclear copper(II) complexes with the anti-inflammatory drug Fenoprofen [Hfen, 2-(3-phenoxyphenyl)propionic acid] and nitrogen donors of general formula [Cu₂(fen)₄(L)] _n were prepared from [Cu₂(fen)₄(dmf)₂]·2H₂O (1) [dmf?=?N,N′-dimethylformamide; L?=?4,4′-bipyridine (2), pyrazine (3), and 2,5-dimethylpyrazine (4)]. The new complexes were characterized by chemical analysis, spectroscopic, and thermogravimetric techniques. Antioxidant properties of 1–4 were evaluated for superoxide-dismutase-mimic activity employing the XTT method. Complex 2 presented the highest antioxidant activity (IC₅₀?=?0.260?µmol?L^?1). Anti-inflammatory properties of 2 were evaluated employing carrageenan-induced paw edema in mice, revealing that the Fenoprofen–copper(II) complex containing 4,4′-bipyridine does not present enhanced anti-inflammatory activity compared to the uncomplexed parent drug Fenoprofen calcium salt.     

Synthesis,characterization, and urease inhibitory activity of two copper(II) complexes of cyclohexanecarboxylate

The crystal structures of two copper(II) complexes of the cyclohexanecarboxylate ligand, namely [Cu(C₆H₁₁CO₂)₂(H₂O)₂]·H₂O (1) and [Cu(dpyam)₂(C₆H₁₁CO₂)](NO₃)·H₂O (2) (C₆H₁₁CO₂H = cyclohexanecarboxylic acid; dpyam = di-2-pyridylamine), have been determined by single-crystal X-ray analysis. Complex 1 contains the square-planar trans-CuO₄ chromophore, while 2 shows the square pyramidal cis-distorted octahedral CuN₄OO′ chromophore. Both complexes were found to show strong inhibitory activity against jack bean urease (IC₅₀ = 1.75 and 8.57 μM for 1 and 2, respectively), when compared with acetohydroxamic acid (IC₅₀ = 63.12 μM).     

Cytotoxicity,apoptosis, interaction with DNA,cellular uptake,and cell cycle arrest of ruthenium(II) polypyridyl complexes containing 4,4′-dimethyl-2,2′-bipyridine as ancillary ligand

Two new ruthenium(II) polypyridyl complexes, [Ru(dmb)₂(DNPIP)](ClO₄)₂ (1) (DNPIP?=?2-(2,4-dinitrophenyl)imidazo[4,5-f][1,10]phenanthroline, dmb?=?4,4′-dimethyl-2,2′-bipyridine) and [Ru(dmb)₂(DAPIP)](ClO₄)₂ (2) (DAPIP?=?2-(2,4-diaminophenyl)imidazo[4,5f][1,10]phenanthroline), were synthesized and characterized. The DNA-binding behaviors of these complexes have been studied by UV-Vis absorption titration, viscosity measurements, and photocleavage. The DNA-binding constants are 7.39 (±0.16)?×?10⁴ (s?=?2.68) and 2.73 (±0.16)?×?10^4?(mol?L^?1)^?1 (s?=?0.64) for 1 and 2, respectively. Their evaluation as cytotoxic agents on different cancer cell lines was investigated with IC₅₀ values of 59.5, 51.3, and 70.3?µmol?L^?1 for 1, >100, 87.9, and 77.9?µmol?L^?1 for 2 against BEL-7402, HepG-2, and MCF-7 cells, respectively. Complex 1 is more active than 2 against selected cancer cell lines. The apoptosis induced by these complexes was studied. Cellular uptake showed that these complexes could enter into the cytoplasm and accumulate in the nuclei. The cell cycle arrest and antioxidant activity against hydroxyl radicals were also investigated.     

Syntheses,characterizations, crystal structures,antibacterial and SOD-like activities of nickel(II) and copper(II) complexes with 2-((Z)-(4-methoxyphenylimino)methyl)-4,6-dichlorophenol

Three mononuclear nickel(II) and copper(II) complexes, [Ni(L)₂(py)₂] (1), [Ni(L)₂(DMF)(H₂O)] (2), and [Cu(L)₂] (3), where HL = 2-((Z)-(4-methoxyphenylimino)methyl)-4,6-dichlorophenol, py = pyridine and DMF = N,N-dimethylformamide, have been synthesized and their structures determined by single crystal X-ray analysis. Complexes 1–3 crystallized in the monoclinic system of the space groups C2/c, P2_1/n, and P2_1/c, respectively. The crystal structures of 1 and 2 present an octahedral geometry at the metal center and 3 shows a square-planar geometry. The FT-IR spectra, UV–vis spectra, and magnetic susceptibility measurements agree with the observed crystal structures. EPR spectra indicate a d_x2–y2 ground state (g_|| > g_⊥ > 2.0023 and A_|| > A_⊥) for 3 at RT and LNT. The results of simultaneous TG-DTA analyses of 1 and 3 showed the final degradation products are NiO for 1 and CuO for 3. The Schiff base (HL) behaves as monobasic bidentate ligand possessing N and O donor atoms. Electrochemical properties for the complexes are similar and involve two irreversible redox processes. Complex 3 exhibits the ability to inhibit jack bean urease, although its Schiff base has no ability to inhibit urease. Complex 1 exhibits more active scavenging effects against O₂^? than HL, 2 and 3 under the same conditions. Antibacterial screening activities of these complexes were also investigated.     

Crystal structure,DNA interaction,and antiproliferative activity of the cobalt(II) complex of demethylcantharate and imidazole

A new cobalt(II) complex, [Co(C₃H₄N₂)(C₈H₈O₅)(H₂O)₂]·2H₂O, of demethylcantharate(7-oxabicyclo[2,2,1]heptane-2,3-dicarboxylate, C₈H₈O₅) with imidazole has been synthesized from cobalt chloride, demethylcantharidin (NCTD) and imidazole. The complex was characterized by elemental analysis, IR, and X-ray single crystal diffraction. The complex crystallized in the monoclinic crystal system and P2₁/m space group with a?=?0.634790(10)?nm, b?=?0.963030(10)?nm, c?=?1.221770(10)?nm, α?=?90°, β?=?95.9700(10)°, γ?=?90°, V?=?0.742844(15)?nm³, M_r ?=?383.22, D_c ?=?1.713?g?cm^?3, Z?=?2, F(0?0?0)?=?398, μ?=?1.206?mm^?1, the final R?=?0.0291, and wR?=?0.0837 [I?>?2σ(I?)]. The interaction of the complex with deoxyribonucleic acid (DNA) was studied by electronic absorption spectra, fluorescence spectra, and viscosity measurements, which indicate that the complex binds to calf thymus DNA through a partially intercalative mode. The binding constant K _b for the complex was 2.62?×?10⁴?L?mol^?1. The antiproliferation activity test showed that the complex has high antiproliferative ability against human hepatoma cells SMMC7721 (with IC₅₀ being 42.8?±?0.9?µmol?L^?1) and human lung cancer cells A549 (with IC₅₀ being 65.1?±?3.2?µmol?L^?1). The inhibition rates of the complex are much higher than those of NCTD.     

Syntheses,crystal structures,and Jack bean urease inhibitory activities of copper(II) complexes derived from 4-tert-butyl-N′-(1-(pyridin-2-yl)ethylidene)benzohydrazide

Two new copper(II) complexes, [CuL(HL)]·ClO₄ (1) and [Cu₂Br₂L₂]·0.85H₂O (2), where L is the monoanionic form of 4-tert-butyl-N′-(1-(pyridin-2-yl)ethylidene)benzohydrazide (HL), have been prepared. The complexes were characterized by infrared and UV–vis spectra, and single crystal X-ray diffraction. Complex 1 is a mononuclear copper(II) species and 2 is a bromido-bridged dinuclear copper(II) species. The Cu ion in 1 is in an octahedral coordination mode and that in 2 is trigonal-bipyramidal. The Jack bean urease inhibitory assay indicated that 2 is active, with IC₅₀ value of 20.6 ± 2.3 μmol L^?1, while 1 is inactive. Molecular docking of 2 with Jack bean urease was studied.     

Synthesis,structure, and biological evaluation of three Cu(II) and Ni(II) (E)-3-(3,4-dimethoxyphenyl)acrylate complexes with organic diamines as potential urease inhibitors

Three new complexes (1–3) have been synthesized and characterized by X-ray single crystal determination and evaluated for inhibitory activity on jack bean urease. All the complexes contained a new cinnamic acid derivative as the ligand (C₁₁H₁₂O₄), (E)-3-(3,4-dimethoxyphenyl)acrylic acid, and crystallized in monoclinic C2/c space group. Complex 1 (C₁₁H₁₁O₄)₄(C₃N₂H₈)₂Cu₂ (C₃N₂H₈?=?1,2-diaminopropane) was obtained with a?=?20.488(2), b?=?19.596(2), c?=?15.2500(13), β?=?93.502(2)°, V?=?6111.2(10)?ų, Z?=?4, R ₁ ?=?0.0616, and wR ₂ ?=?0.2059. Complex 2 (C₁₁H₁₁O₄)₄(C₃N₂H₈)₂Cu₂ (C₃N₂H₈=1,3-diaminopropane) was obtained with a?=?20.2494(12), b?=?19.5732(12), c?=?14.8940(8), β?=?96.884(2)°, V?=?5860.6(6)?ų, Z?=?4, R ₁ ?=?0.0409, and wR ₂ ?=?0.1107. Complex 3 (C₁₁H₁₁O₄)₂(C₂N₂H₆)₂Ni₂·H₂O (C₂N₂H₆?=?ethylenediamine) was obtained with a?=?28.359(2), b?=?6.5422(5), c?=?16.8587(14), β?=?101.359(2)°, V?=?3066.5(4)?ų, Z?=?4, R ₁ ?=?0.0422, and wR ₂ ?=?0.1190. It was found that copper(II) complexes 1 [IC₅₀?=?4.71?μM] and 2 [IC₅₀?=?3.15?μM] showed strong inhibitory activity against jack bean urease compared with acetohydroxamic acid [IC₅₀?=?10.01?μM] as a positive reference. Unfortunately, 3 exhibited no inhibitory activity.     

Syntheses,urease inhibition activities,and fluorescent properties of transition metal complexes

Four transition metal complexes with Schiff base and 1,10-phenanthroline, [Cu(L)(phen)]₂·C₂H₅OH (1), [Zn(L)(phen)]₂·C₂H₅OH (2), [Ni(L)(phen)]₂·C₂H₅OH (3), and [Co(L)(phen)]₂·C₂H₅OH (4) (H₂L?=?1-((2-hydroxynaphthalen-1-yl)methylene)thiosemicarbazide; phen?=?1,10-phenanthroline) were synthesized and characterized by physico-chemical methods. The crystal structure of 1 was determined by X-ray single-crystal diffraction analysis. 1 crystallizes in the orthorhombic space group Pbca with a?=?15.008(9), b?=?16.100(10), c?=?37.54(2)?Å, V?=?9070(10)?ų, Z?=?8, GOOF?=?1.002, R ₁?=?0.0626, and wR ₂?=?0.0912. The fluorescence and urease inhibitory activities of the compounds were tested. The enzymatic activity study indicated that 3 possessed potent inhibition against jack bean urease, with IC₅₀?=?1.2?±?0.1?μM, and about 35 times more than 42.1?±?0.4 acetohydroxamic acid as positive reference. This suggests that inhibitory efficiency of these complexes can be strongly influenced by different transition metal ions.     

Synthesis,structure, and urease inhibitory activities of Co(III), Mn(II) and Zn(II) complexes with hydrazone derived from protocatechuic acid

[Co^III(L₁)₂·H₂O]NO₃ (1), [Mn^II(L₁)₂·H₂O] (2), and [Zn^II(L₁)₂·H₂O] (3) with a hydrazone derived from protocatechuic acid (HL₁ = C₁₅H₁₃N₃O₃) were designed, synthesized, and characterized by C, H, N elemental analyses, single-crystal X-ray diffraction, and IR spectra, which revealed that the three complexes are similar structures. Docking study has been done. The urease inhibitory activities of the three complexes were tested. Complexes 1 and 3 showed strong inhibitory activity against jack bean urease with IC₅₀ values of 45.9 and 11.64 μM. Complex 2 had no obvious inhibitory activity to urease; the IC₅₀ was > 50 μM.     

Theoretical,antimicrobial, antioxidant,in vitro cytotoxicity,and cyclin-dependent kinase 2 inhibitor studies of metal(II) complexes with bis(imidazol-1-yl)methane-based heteroscorpionate ligands

Abstract

A series of C-centered heteroscorpionate-based homoleptic manganese(II), nickel(II), and copper(II) complexes of type [M(L^1–3)₂] (1–9) have been synthesized by using the ligands (2-hydroxyphenyl)bis(imidazol-1-yl)methane (HL¹), (4-diethylamino-2-hydroxyphenyl)bis(imidazol-1-yl)methane (HL²) and (5-bromo-2-hydroxyphenyl)bis(imidazol-1-yl)methane (HL³). The geometric parameters of the complexes were determined using UV-vis and theoretical studies suggesting distorted octahedral geometry around metal(II) ion. Frontier molecular orbital analysis supports bioefficacy of the complexes. Antimicrobial activity of the metal(II) complexes were determined against two Gram(–ve) (Escherichia coli and Klebsiella pneumoniae) and two Gram(+ve) (Bacillus cereus and Staphylococcus aureus) bacteria, and three fungal (Candida albicans, Candida glabrata, and Candida krusei) strains. Antioxidant activity of nickel(II) and copper(II) complexes were evaluated against ABTS, DPPH, and H₂O₂ free radicals. In vitro cytotoxicity activity of nickel(II) and copper(II) complexes against human breast adenocarcinoma (MCF-7), cervical (HeLa), and lung (A549) cancer cell lines along with one normal human dermal fibroblasts (NHDF) cell line were carried out by MTT assay, which shows the potent activity of copper(II) complex 8 with respect to the standard drug cisplatin. Molecular docking studies evidence the interaction of complexes with cyclin-dependent kinase 2 receptor (CDK2).     

Synthesis,crystal structures and Jack bean urease inhibitory activity of copper(II) complexes with 4-bromo-N′-(2-hydroxy-5-methoxybenzylidene)benzohydrazide

A new hydrazone 4-bromo-N′-(2-hydroxy-5-methoxybenzylidene)benzohydrazide (HL) was prepared and characterized by infrared and UV–vis spectra, as well as single-crystal X-ray diffraction. With the hydrazone as ligand, two new copper(II) complexes were prepared, [Cu₂L₂(NCS)₂]·4H₂O (1) and [CuBrL]·CH₃OH (2). The complexes were characterized by infrared and UV–vis spectra, and single-crystal X-ray diffraction. The Cu in 1 is in a square pyramidal coordination geometry and that in 2 is in a square planar coordination geometry. The two complexes show effective Jack bean urease inhibitory activity, with IC₅₀ values of 23.5 and 2.7 μM, respectively. A molecular docking study of 2 with the urease was performed. The relationship between the structure and urease inhibitory activity indicated that copper complex with square planar coordination is a better model for urease inhibition.     

Design and synthesis of fluorescent symmetric bis-triazolylated-1,4-dihydropyridines as potent antibreast cancer agents

Herein, we report the synthesis of fluorescent 1,4-dihydropyridine-linked bis-triazoles (2a–2n) through Hantzsch synthesis by the condensation of o/m-chloro-substituted benzaldehyde, ethyl 3-oxo-4(prop-2-yn-1-yloxy)butanoate, and ammonium acetate in the presence of Ba(NO₃)₂ as a catalyst followed by the click reaction of resultant Hantzsch product (1) with various aromatic as well as aliphatic azides. All the synthesized compounds were well characterized by ¹H-NMR, ¹³C-NMR, FTIR, and HRMS spectral techniques. Antibreast cancer evaluation of all the synthesized derivatives revealed that the compounds 2f (IC₅₀?=?7?±?0.02?µM) and 2g (IC₅₀?=?5?±?0.03?µM) showed better anticancer activity (lower IC₅₀) than the standard drug tamoxifen (IC₅₀?=?11.2?±?0.01?µM) against breast carcinoma (MDA-MB-231) cell line. The synthesized compounds were also screened against normal human embryonic kidney (HEK-293) cell line and found to be nontoxic. The fluorescent nature and cytotoxicity assay of these newly synthesized hybrids recommend their utility in tumor cell imaging.     

Synthesis,structure and antimicrobial study of two new copper(II) complexes derived from N-(3-aminopropyl) benzylamine ligand (apba) and N-salicylidene-apba

Two new copper(II) complexes were synthesized by reaction of N-(3-aminopropyl)benzylamine (L1: apba, for complex 1) and N-salicylidene-apba (L2: for complex 2) with Cu²⁺. Crystals of complex 1 were orthorhombic, space group pccn, with a?=?15.2149(10), b?=?25.0071(16), c?=?7.6280(5)?Å and α?=?β?=?γ?=?90°. Complex 2 crystals were monoclinic, space group P2₁/c, with a?=?8.688(6), b?=?12.812(9), c?=?16.022(11)?Å and β?=?99.241(10)°. Structures of the two complexes were centro-symmetric and both Cu(II) atoms were four coordinate with a distorted square-planar geometry. The toxicity of the complexes was evaluated by testing antimicrobial activity against bacterial strands.     

Synthesis,molecular docking,and inhibitory activity of a Ni Schiff-base complex against urease

A Ni(II) Schiff-base complex, Ni(C₁₄H₁₀NOBr₂)₂, was synthesized and structurally characterized by single-crystal X-ray analysis. Its inhibitory activity against Helicobacter pylori urease was evaluated in vitro and showed strong inhibitory activity against H. pylori urease compared with acetohydroxamic acid (IC₅₀ = 42.12 µmol L^?1), which is a positive reference. A docking analysis using the autodock 4.0 program could explain the inhibitory activity of the complex against urease.