Dataset Information

Design, Synthesis, and Biological Evaluation of Benzimidazole-Derived Biocompatible Copper(II) and Zinc(II) Complexes as Anticancer Chemotherapeutics.

ABSTRACT: Herein, we have synthesized and characterized a new benzimidazole-derived "BnI" ligand and its copper(II) complex, [Cu(BnI)?], 1, and zinc(II) complex, [Zn(BnI)?], 2, using elemental analysis and various spectroscopic techniques. Interaction of complexes 1 and 2 with the biomolecules viz. HSA (human serum albumin) and DNA were studied using absorption titration, fluorescence techniques, and in silico molecular docking studies. The results exhibited the significant binding propensity of both complexes 1 and 2, but complex 1 showed more avid binding to HSA and DNA. Also, the nuclease activity of 1 and 2 was analyzed for pBR322 DNA, and the results obtained confirmed the potential of the complexes to cleave DNA. Moreover, the mechanistic pathway was studied in the presence of various radical scavengers, which revealed that ROS (reactive oxygen species) are responsible for the nuclease activity in complex 1, whereas in complex 2, the possibility of hydrolytic cleavage also exists. Furthermore, the cytotoxicity of the ligand and complexes 1 and 2 were studied on a panel of five different human cancer cells, namely: HepG2, SK-MEL-1, HT018, HeLa, and MDA-MB 231, and compared with the standard drug, cisplatin. The results are quite promising against MDA-MB 231 (breast cancer cell line of 1), with an IC50 value that is nearly the same as the standard drug. Apoptosis was induced by complex 1 on MDA-MB 231 cells predominantly as studied by flow cytometry (FACS). The adhesion and migration of cancer cells were also examined upon treatment of complexes 1 and 2. Furthermore, the in vivo chronic toxicity profile of complexes 1 and 2 was also studied on all of the major organs of the mice, and found them to be less toxic. Thus, the results warrant further investigations of complex 1.

SUBMITTER: AlAjmi MF

PROVIDER: S-EPMC5983663 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Design, Synthesis, and Biological Evaluation of Benzimidazole-Derived Biocompatible Copper(II) and Zinc(II) Complexes as Anticancer Chemotherapeutics.

AlAjmi Mohamed F MF Hussain Afzal A Rehman Md Tabish MT Khan Azmat Ali AA Shaikh Perwez Alam PA Khan Rais Ahmad RA

International journal of molecular sciences 20180516 5

Herein, we have synthesized and characterized a new benzimidazole-derived "BnI" ligand and its copper(II) complex, [Cu(BnI)₂], 1, and zinc(II) complex, [Zn(BnI)₂], 2, using elemental analysis and various spectroscopic techniques. Interaction of complexes 1 and 2 with the biomolecules viz. HSA (human serum albumin) and DNA were studied using absorption titration, fluorescence techniques, and in silico molecular docking studies. The results exhibited the significant bin ...[more]

PMID: 29772746

Similar Datasets

Project description:Three new transition metal complexes, Cu(II) 1, Co(II) 2, and Zn(II) 3 with ligand “bimnap” derived from 1-methyl-2-aminobenzimidazole and 2-hydroxynapthaldehyde were synthesized and characterized. The structure of the ligand was determined by single X-ray crystallography. All the three complexes, 1⁻3, were examined for the mode of interaction with biomolecule viz., calf thymus-DNA (CT-DNA) using various spectroscopic methods. The nuclease activity was performed against pBR322 DNA that exhibited concentration-dependent degradation of the nucleic acid. The mechanism of DNA cleavage was studied by the electrophoretic pattern in the presence of the radical scavengers. Also, the complexes 1⁻3 were analyzed for groove binding affinity. Moreover, in vitro cytotoxicities of the complexes 1⁻3 were tested against the five human cancer cell lines, i.e., HeLa, SK-MEL-1, HepG2, HT108, and MDA-MB 231. Also, the cell adhesion and migration properties upon treatment of cell lines with complexes 1⁻3, and consequently, their cell death pathway via apoptosis and necrosis were analyzed. Further, complexes 1⁻3 were studied in vivo for their toxicities and tolerabilities in mice. In sum, the complexes 1⁻3 showed merits of an effective anticancer agent in cell lines⁻based study while minor side effects were observed in vivo.A green solvent extraction technology involving a microwave processing method was used to increase the content of minor ginsenosides from Panax notoginseng. This article aims to investigate the optimization of preparation of the minor ginsenosides by this microwave processing method using single-factor experiments and response surface methodology (RSM), and discuss the blood-enriching activity and hemostatic activity of the extract of microwave processed P. notoginseng (EMPN) The RSM for production of the minor ginsenosides was based on a three-factor and three-level Box-Behnken design. When the optimum conditions of microwave power, temperature and time were 495.03 W, 150.68 °C and 20.32 min, respectively, results predicted that the yield of total minor ginsenosides (Y₉) would be 93.13%. The actual value of Y₉ was very similar to the predicted value. In addition, the pharmacological results of EMPN in vivo showed that EMPN had the effect of enriching blood in N-acetylphenylhydrazine (APH) and cyclophosphamide (CTX)-induced blood deficient mice because of the increasing content of white blood cells (WBCs) and hemoglobin (HGB) in blood. Hemostatic activity in vitro of EMPN showed that it had significantly shortened the clotting time in PT testing (p < 0.05). The hemostatic effect of EMPN was mainly caused by its components of Rh₄, 20(S)-Rg₃ and 20(R)-Rg₃. This microwave processing method is simple and suitable to mass-produce the minor ginsenosides from P. notoginseng.

Project description:Interest is increasingly focused on the use of transition metal complexes as biochemical, medical, analytical, pharmaceutical, agronomic, anticancer, and antibacterial agents. In this study, three complexes of [Zn(H2L)Cl] (1), [Cu(H2L)(H2O)(NO3)] (2) and [Ni(H2L)(NO3)].2H2O (3) were synthesized from a 2-chloroquinoline-3-carbaldehyde derived ligand [H3L = ((E)-2-(((2-((2-hydroxyethyl)amino)quinolin-3-yl)methylene)amino)ethanol. The compounds were characterized using physicochemical and spectroscopic methods. The results demonstrate that the free ligand behaves as a tridentate ligand with one oxygen and two nitrogen (ONN) donor atoms in 1:1 metal:ligand ratio. The formation constants of the complexes were found to be (K Zn(II) = 2.3 × 106, K Cu(II) = 2.9 × 106, and K Ni(II) = 3.8 × 105). The thermodynamic parameters indicated that the reactions were spontaneous with exothermic nature of metal-ligand interaction energies. Based on the analyses of the experimental (EDX, FTIR, PXRD, MS and TGA) and DFT results, a distorted tetrahedral, a distorted square pyramidal and square planar geometry for Zn(II), Cu(II) and Ni(II) complexes, respectively, were proposed. The B3LYP calculated IR frequencies and TD-B3LYP calculated absorption spectra were found to be in good agreement with the corresponding experimental results. The powder XRD data confirmed that the Zn(II), Cu(II) and Ni(II) complexes have polycrystalline nature with average crystallite sizes of 27.86, 33.54, 37.40 Å, respectively. In vitro antibacterial activity analyses of the complexes were studied with disk diffusion method, in which the complexes showed better activity than the precursor ligand. Particularly the Cu(II) complex showed higher percent activity index (62, 90%), than both Zn(II) (54, 82%) and Ni(II) (41, 68%) complexes against both E. coli and P. aeruginosa, respectively. Using the DPPH assay, the complexes were further assessed for their antioxidant capacities. All metal complexes showed improved antioxidant activity than the free ligand. Zn(II) and Cu(II) complexes, which had IC50 values of 10.46 and 8.62 μg/ml, respectively, showed the best antioxidant activity. The calculated results of Lipinski's rule of five also showed that the target complexes have drug-like molecular nature and similarly, the results of binding mode of action of these compounds against E. coli DNA gyrase B and P. aeruginosa LasR.DNA were found to be in good agreement with the in vitro biological activities.

Project description:Synthesis, characterization, reactivity, and sensing properties of 4-formylbenzoate complexes of copper(II), zinc(II), and cadmium(II) possessing the 1,10-phenanthroline ancillary ligand are studied. The crystal structures of the (1,10-phenanthroline)bis(4-formylbenzoate)(aqua)copper(II) and (1,10-phenanthroline)bis(4-formylbenzo-ate)zinc(II) and a novel molecular complex comprising an assembly of mononuclear and dinuclear species of (1,10-phenanthroline)bis(4-formylbenzoate)cadmium(II) are reported. These zinc and cadmium complexes are fluorescent; they show differentiable sensitivity to detect three positional isomers of nitroaniline. The mechanism of sensing of nitroanilines by 1,10-phenanthroline and the complexes are studied by fluorescence titrations, photoluminescence decay, and dynamic light scattering. A plausible mechanism showing that 1,10-phenanthroline ligand-based emission quenched by electron transfer from the excited state of 1,10-phenanthroline to nitroaniline is supported by density functional theory calculations. In an anticipation to generate a fluorescent d10-copper(I) formylbenzoate complex by a mild reducing agent such as hydroxylamine hydrochloride for similar sensing of nitroaromatics as that of the d10-zinc and cadmium 4-formylbenzoate complexes, reactivity of d9-copper(II) with hydroxylamine hydrochloride in the presence of 4-formylbenzoic acid and 1,10-phenanthroline is studied. It did not provide the expected copper(I) complex but resulted in stoichiometry-dependent reactions of 4-formylbenzoic acid with hydroxylamine hydrochloride in the presence of copper(II) acetate and 1,10-phenanthroline. Depending on the stoichiometry of reactants, an inclusion complex of bis(1,10-phenanthroline)(chloro)copper(II) chloride with in situ-formed 4-((hydroxyimino)methyl)benzoic acid or copper(II) 4-(hydroxycarbamoyl)benzoate complex was formed. The self-assembly of the inclusion complex has the bis(1,10-phenanthroline)(chloro)copper(II) cation encapsulated in hydrogen-bonded chloride-hydrate assembly with 4-((hydroxyimino)methyl)benzoic acid.

Project description:We report the synthesis and characterization of a group of benzoylhydrazones (Ln) derived from 2-carbaldehyde-8-hydroxyquinoline and benzylhydrazides containing distinct para substituents (R = H, Cl, F, CH3, OCH3, OH and NH2, for L1-7, respectively; in L8 isonicotinohydrazide was used instead of benzylhydrazide). Cu(II) complexes were prepared by reaction of each benzoylhydrazone with Cu(II) acetate. All compounds were characterized by elemental analysis and mass spectrometry as well as by FTIR, UV-visible absorption, NMR or electron paramagnetic resonance spectroscopies. Complexes isolated in the solid state (1-8) are either formulated as [Cu(HL)acetate] (with L1 and L4) or as [Cu(Ln)]3 (n = 2, 3, 5, 6, 7 and 8). Single crystal X-ray diffraction studies were done for L5 and [Cu(L5)]3, confirming the trinuclear formulation of several complexes. Proton dissociation constants, lipophilicity and solubility were determined for all free ligands by UV-Vis spectrophotometry in 30% (v/v) DMSO/H2O. Formation constants were determined for [Cu(LH)], [Cu(L)] and [Cu(LH-1)] for L = L1, L5 and L6, and also [Cu(LH-2)] for L = L6, and binding modes are proposed, [Cu(L)] predominating at physiological pH. The redox properties of complexes formed with L1, L5 and L6 are investigated by cyclic voltammetry; the formal redox potentials fall in the range of +377 to +395 mV vs. NHE. The binding of the Cu(II)-complexes to bovine serum albumin was evaluated by fluorescence spectroscopy, showing moderate-to-strong interaction and suggesting formation of a ground state complex. The interaction of L1, L3, L5 and L7, and of the corresponding complexes with calf thymus DNA was evaluated by thermal denaturation. The antiproliferative activity of all compounds was evaluated in malignant melanoma (A-375) and lung (A-549) cancer cells. The complexes show higher activity than the corresponding free ligand, and most complexes are more active than cisplatin. Compounds 1, 3, 5, and 8 were selected for additional studies: while these complexes induce reactive oxygen species and double-strand breaks in both cancer cells, their ability to induce cell-death by apoptosis varies. Within the set of compounds tested, 8 emerges as the most promising one, presenting low IC50 values, and high induction of oxidative stress and DNA damage, which eventually lead to high rates of apoptosis.

Dataset Information

Design, Synthesis, and Biological Evaluation of Benzimidazole-Derived Biocompatible Copper(II) and Zinc(II) Complexes as Anticancer Chemotherapeutics.

Publications

Design, Synthesis, and Biological Evaluation of Benzimidazole-Derived Biocompatible Copper(II) and Zinc(II) Complexes as Anticancer Chemotherapeutics.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets