ABSTRACT
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.
ABSTRACT
In the present work, two novel complexes of zinc(II) and copper(II) were synthesized from the ligand 2-((2-hydroxyethyl)amino)quinoline-3-carbaldehyde (H 2 L) in a 1:2 metal-to-ligand ratio in methanol. The complexes were characterized by UV-visible spectroscopy, fluorescence spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (XRD), scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDX), mass spectrometry (MS), nuclear magnetic resonance (NMR) spectroscopy, and thermogravimetric analysis (TGA) experimental techniques and density functional theory (DFT) calculations. The spectral data revealed that the mono-deprotonated (HL) ligand acted as a bidentate ligand, which bound to both Zn(II) and Cu(II) ions via the nitrogen atom of the amine (N-H) and the hydroxyl (O-H) groups through the deprotonated oxygen atom. Formation constants and thermal analysis indicated that both metal complexes are stable up to 100 °C with thermodynamically favored chemical reactions. The Cu(II) complex showed antibacterial activities with the zones of inhibition of 20.90 ± 2.00 mm against Pseudomonas aeruginosa, 19.69 ± 0.71 mm against Staphylococcus aureus, and 18.58 ± 1.04 mm against Streptococcus pyogenes. These results are relatively higher compared with the Zn(II) complex at the same concentration. The minimum inhibitory concentration (MIC) results for the complexes also showed similar trends against the three bacteria. On the other hand, radical scavenging activities of both Cu(II) and Zn(II) complexes showed half-maximal inhibitory concentrations (IC50) of 4.72 and 8.2 µg/mL, respectively, while ascorbic acid (a positive control) has a value of 4.28 µg/mL. The Cu(II) complex exhibited better communication with the positive control, indicating its potential use for biological activities. The calculated and in silico molecular docking results also strongly support the experimental results.
ABSTRACT
Herein, we report novel Co(II) and V(IV) complexes synthesized from an (E)-2-(((2-((2-hydroxyethyl)amino)quinolin-3-yl)methylene)amino)ethan-1-ol ligand (L), cobalt(II) chloride hexahydrate, and vanadyl(IV) sulfate in methanolic solutions. The ligand and the complexes were characterized by 1H NMR spectroscopy,13C NMR spectroscopy, UV-visible spectroscopy, fluorescence spectroscopy, FT-IR spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX), mass spectroscopy (MS), thermal analysis, and molar conductance. The FT-IR spectral data showed that the ligand adopted a tridentate fashion when binding with the metal ions via the nitrogen atoms of the imine (C=N) and amine (N-H), and the oxygen atom of the hydroxyl group (O-H). The PXRD and SEM results indicated that the complexes are amorphous in nature. The density functional theory (DFT) calculated absorption and IR spectra agree very well with the corresponding experimental results. The antibacterial activities of the free ligand and its complexes were evaluated using a paper disk diffusion method. The complexes have better percent activitiy index than the free ligand. The cobalt complex exhibited a more recognizable antibacterial activity than the vanadium complex, specifically against Pseudomonas aeruginosa with a mean inhibition zone of 18.62 ± 0.19 mm, when compared with the positive control, ciprofloxacin, with a mean inhibition zone of 22.98 ± 0.08 mm at the same concentration. Furthermore, the antioxidant activities of the free ligand and its metal complexes were also determined in vitro using 2,2-diphenyl-1-picrylhydrazyl. The ligand exhibited less in vitro antioxidant activity than its transition metal complexes, in which the cobalt complex has a better antioxidant activity with half-inhibitory concentrations (IC50 of 16.01 µg/mL) than the ligand and the vanadium complex. Quantum molecular descriptors from the DFT calculations further support the experimental results. Molecular docking analysis also shed more light on the biological activities of the novel cobalt and vanadium complexes.
ABSTRACT
BACKGROUND: Quinolines have demonstrated various biological activities such as antimalarial, antibacterial and anticancer. Hence, compounds with such scaffold have been used as lead in drug development. This project is, therefore, aimed to synthesis and evaluates some biological activities of quinoline analogs. METHODS: 2-Chloro-7-fluoroquinoline-3-carbaldehydes were synthesized by the application of Vilsmeier-Haack reaction. The chlorine in the fluoroquinoline-3-carbaldehyde was replaced with various nucleophiles. The aldehyde functional group was also converted to carboxylic acid and imine groups using oxidizing agent and various amines, respectively. The structures of the compounds synthesized were characterized by spectroscopic methods. Disc diffusion and DPPH assays were used to evaluate the antibacterial and antioxidant activities, respectively. The in silico molecular docking analysis of the synthesized compounds were done using AutoDock Vina against E. coli DNA Gyrase B and human topoisomerase IIα. The drug likeness properties were assessed using SwissADME and PreADMET. RESULTS: Nine novel quinoline derivatives were synthesized in good yields. The in vitro antibacterial activity of the synthesized compounds was beyond 9.3 mm inhibition zone (IZ). Compounds 4, 5, 6, 7, 8, 10, 15, and 16 exhibited activity against E. coli, P. aeruginosa, S. aureus and S. pyogenes with IZ ranging from 7.3 ± 0.67 to 15.3 ± 0.33 mm at 200 µg/mL. Compound 9 displayed IZ against three of the bacterial strains except S. aureus. The IC50 for the radical scavenging activity of the synthesized compounds were from 5.31 to 16.71 µg/mL. The binding affinities of the synthesized compounds were from - 6.1 to - 7.2 kcal/mol against E. coli DNA gyrase B and - 6.8 to - 7.4 kcal/mol against human topoisomerase IIα. All of the synthesized compounds obeyed Lipinski's rule of five without violation. CONCLUSION: Compounds 4, 5, 6, 7, 8, 10, 15, and 16 displayed activity against Gram positive and Gram negative bacterial strains indicating that these compounds might be used as broad spectrum bactericidal activity. Compound 8 (13.6 ± 0.22 mm) showed better IZ against P. aeruginosa compared with ciprofloxacin (10.0 ± 0.45 mm) demonstrating the potential of this compound as antibacterial agent against this strain. Compounds 5, 6, 7, 8, 9 and 10 showed comparable binding affinities in their in silico molecular docking analysis against E. coli DNA gyrase B. All of the synthesized compounds also obeyed Lipinski's rule of five without violation which suggests these compounds as antibacterial agents for further study. Compounds 7 and 8 were proved to be a very potent radical scavenger with IC50 values of 5.31 and 5.41 µg/mL, respectively. Compound 5, 6, 8, 10 and 16 had comparable binding affinity against human topoisomerase IIα suggesting these compounds as a possible candidate for anticancer drugs.
