Synthesis, characterization, and molecular docking analysis of novel benzimidazole derivatives as cholinesterase inhibitors (original) (raw)
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Chemistry Africa, 2023
Inhibition of bacterial infectious diseases is one feature of transition metal complexes. However, identifying the right metal to ligand combination, which is physiologically signifcant, is the key condition to get the therapeutic property. To this end, a new complex [Co(Phen)2(Ad)(Ac)]Cl2⋅0.5H2O (3) was prepared from previously reported complexes, namely, [Co(Phen)2(H2O)2]Cl2⋅0.5H2O (1) and [Co(Phen)2(H2O)Ad]Cl2⋅0.5H2O (2) which were synthesized using CoCl2⋅6H2O, 1,10-phenanthroline (L1), adenine (L2) and acetamide (L3). The prepared complex was investigated using spectroscopic techniques (ESI–MS, pXRD, TGA, CHN elemental analysis, ICP OES, FT-IR and UV–Vis) to check its structure in which an octahedral geometry is proposed. The quantum chemical characteristics of the complexes were studied using density functional theory. The calculated energy gaps for compounds 1 (4.218 eV), 2 (3.953 eV), and 3 (3.038 eV) suggest that the newly synthesized complex 3 has good chemical reactivity. The complexes’ in vitro antibacterial activities were tested on two Gram-positive [Streptococcus pyogenes (S. pyogenes)] and [Staphylococcus aureus (S. aureus)] and two Gram-negative [Escherichia coli (E. coli)] and [Klebsiella pneumoniae (K. pneumonia)] bacteria. The results showed that the activities of all the complexes are better than L2 and L3. The molecular docking studies showed that all the complexes exhibit good binding affinities 1 (−6.42 kcal/mol), 2 (−7.70 kcal/mol), and 3 (−8.93 kcal/mol) against the active sites of K. pneumoniae (PDB ID: 6rd3). Furthermore, the precursors and the new complex are water soluble and the water solubility of the compound could be evaluated as an opportunity for biomedical applications.
Frontiers in chemistry, 2024
The present work reports the influence of the presence of different ions (Cl − , Br − , NO 3 − , or SO 4 2−) on the formation and proprieties of Cu(II) complexes with pyridoxal-benzoylhydrazone (PLBHZ). Four new complexes were successfully synthesized, [CuCl 2 (PLBHZ)] (1), [CuBr 2 (PLBHZ)] (2), [CuCl(PLBHZ)H 2 O]•NO 3 •H 2 O (3), and [CuSO 4 (PLBHZ)H 2 O]•3H 2 O (4), and characterized by spectroscopic and physicochemical methods. A single-crystal X-ray study reveals the Schiff base coordinated to the metal center tridentate by the ONS-donor system, resulting in distorted square pyramidal coordination geometries. Noncovalent interactions were investigated by 3D Hirshfeld surface analysis by the d norm function, 2D fingerprint plots, and full interaction maps. The ion exchange is important in forming three-dimensional networks with π•••π stacking interactions and intermolecular hydrogen bonds. The in vitro biological activity of the free ligand and metal complexes was evaluated against Gram-positive and Gramnegative bacterial strains and the free pyridoxal-hydrazone ligand showed higher activity than their Cu(II) complexes. Molecular docking was used to predict the inhibitory activity of the ligand and complexes against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria.
Studies of some metal ions complexes and her antimicrobial activity by DFT and molecular Docking
2015
In court discovering new drugs for the purpose of o ur work is to confirm the tridentate ligand complex ations mechanism 2, 5-Diamino-1, 3, 4-tiadiazole [1] with Co (II), Ni (II) and Cu (II) using the DFT. The met al chelates have antimicrobial activity and for this we studied the molecular docking of these complex and penicil lin binding proteins (PBPs) for the best complex of the enzyme with the metal complex to discover new drugs. Densi ty functional theory (DFT) was used, using the B3LYP f unctional and the 6-31G (d) basis set. This level o f calculation was used to find the complex structure and Fukui fu nction values (NK), Local indices Nk and chemical r eactivity parameters stemming from conceptual DFT and molecul ar docking using the UCSF Chimera software to predi ct the activity antimicrobial of these complexes and also the enzyme. For our work we confirmed the attack si tes for the ligand 2, 5-Diamino-1, 3, 4-tiadiazole using concep tual DFT and for that training octahedra...
Evalution and Molecular Docking of Benzimidazole and its Derivatives as a Potent Antibacterial Agent
Biomedical and Pharmacology Journal, 2019
The study was performed to identify a potent antibacterial benzimidazole derivative using in vitro and in silico techniques. Benzimidazole and its derivatives were synthesized by reflux process. The derivatives were screened for antibiotic susceptibility test (AST) and minimum inhibitory concentration (MIC) against Gram-negative and Gram-positive clinical isolates and compared with the positive control Norfloxacin. Insilico molecular docking was performed to screen the binding potential of the derivatives with target enzymes topoisomerase II /DNA gyraseof Escherichia coli (E.coli) and Staphylococcus aureus (S.aureus) along with the control Norfloxacin.Totally fifty-four isolates were screened for antimicrobial supectibility test (AST) and minimum inhibitory concentration (MIC) and 35 clinical isolates of Gram-negative showed 86% resistance to Norfloxacin and 19 isolates of Gram-positive showed 90% resistance to Norfloxacin. However, these isolates were found to be sensitive to 1-(4-((1H-benzimidazol-1-yl) methylamino) phenyl) ethanone (3) (C2), and 2-methyl-1H-benzimidazole (C4) compounds, with MIC ranges from 6.25-12.5 µg/ml. Molecular docking analysis revealed that the compound C2 exhibited better binding affinity towards topoisomerase II / DNA gyrase of E.coli and S.aureus when compared with C4 and control Norfloxacin. The antibacterial activity of these may due to the inactivation of these enzymes which is supported by the MIC results.The obtained in vitro and in silico results suggested that C2 showed better antimicrobial activity.
Journal of Applied Pharmaceutical Science
New chelates complexes of general formulae [Cr(H 2 L) 2 Cl 3 .EtOH], [Fe(H 2 L)(OH)SO 4 (H 2 O).2H 2 O], [Fe(HL) 2 (OH)]. H 2 O, and [Co(H 2 L)(HL) 2 .1/2 EtOH] were prepared and identified by spectral techniques and thermogravimetric analysis Derivative thermo gravimetric analysis. The results confirmed that the ligand behaved as neutral tetradentate, bidentate, or monobasic tridentate. Coordination has occurred via carbonyl oxygen (C=O) and N(2)H or (C-S) groups in complex (3). Moreover, complex (3) was more stable than the analogs (1-3). The prepared mononuclear complexes exhibited an octahedral conformation. The ligand and Cr(III), Fe(III), and Co(II) complexes were investigated for their inhibitory action on the growth of Streptococcus pyogenes and Escherichia coli as Gram-positive and negative bacteria, respectively. The results indicated the effective behavior of Cr(III), Fe(III), and Co(II) complexes as being antibacterial compared to the ligand. The in vitro antitumor activity also displayed the potent action of compounds. In addition, it was revealed that the majority of complexes were more effective than their free ligand. Furthermore, molecular docking implementation demonstrated the intriguing possible interactions of the ligands and complexes with amino acid active sites of the ribosyltransferase moiety (PDB ID).
Material Science Research India, 2022
The nitrogen containing heterocyclic compounds play a very important role in defining their biological and pharmacological properties. Two such important compounds having known crystal structure, viz.5-Methoxy-1 H-benzo [d] imidazole-2(3H)-thione (M1) and 4, 5-Dimethyl benzimidazolene-2-thione (M2), have been investigated for their optimal molecular geometry, atomic Mulliken charges, molecule electrostatic potential, HOMO (highest occupied molecular orbital)-LUMO (lowest unoccupied molecular orbital), and associated molecular characteristics using DFT (density functional theory). The optimized geometry of (M1) and (M2), slightly deviates from the X-ray structure. The N-H...S and N-H...O hydrogen bonding contribute to the Hirsh feld surface in the molecular structure M1 [24.2 % and 7.1 % of the overall contribution, respectively] while the N-H...S hydrogen bonding contribution is 25.4% in M2. The crystal void analysis has also been reported, besides the energy frameworks built using distinct intermolecular interaction energies. The computational antibacterial activity of both structures has been analyzed in silico with Staphylococcus epidermidis bacterial protein (PDB ID: 4EJV). The results indicate that M1 and M2 possess higher binding energy with more interactions as compared to the standard drug chloramphenicol with receptor complex and this observation leads us to the state that these two derivatives could be the potential candidates for the antibacterial drug development process.
JBIC Journal of Biological Inorganic Chemistry, 2017
Interaction of DNA with free ligand (1a and 2a) is insignificant, while the complexes (1b and 2b) interact strongly and the binding constants are K b , 8.413 × 10 4 M −1 (1b) and 6.56 × 10 5 M −1 (2b). Optimized structures of the compounds are docked with protein structure of DHPS (E. coli) to propose the most favoured binding mode of the drugs in the active site. The in silico test of the compound helps to understand drug metabolism, drug-protein interactions, and toxicity (ADMET).
Applied Organometallic Chemistry, 2017
Co(III) complexes of tridentate Schiff base ligands derived from N-(2hydroxybenzylideneamino)benzamide (H 2 L 1) and 2-(2-hydroxybenzylidene) hydrazine-1-carboxamide (H 2 L 2) were synthesized and characterized using IR, Raman, 1 H-NMR and UV-Vis spectroscopies. X-ray single crystal structures of complexes 1 and 2 have also been determined, and it was indicated that these Co(III) complexes are in a distorted octahedral geometry. The cyclic voltammetry (CV) of the complexes indicates an irreversible redox behavior for both complexes 1 and 2. The antibacterial effects of the synthesized compounds have been tested by minimum inhibitory concentration and minimum bactericidal concentration methods, which suggested that the metal complexes exhibit better antibacterial effects than the ligands against Gram-positive bacteria. The effects of the drug (drug = ligands and complexes) on bovine serum albumin (BSA) were examined using circular dichroism (CD) spectropolarimetry, and it was revealed that the BSA (BSA, as a carrier protein) secondary structure changed in the presence of the drug. Interaction of the drug with calf-thymus DNA (CT-DNA) was investigated by UV-Vis absorption, fluorescence emission, CV and CD spectroscopy. Binding constants were determined using UV-Vis absorption. The results indicated that the studied Schiff bases bind to DNA, with the hyperchromic effect and non-intercalative mode in which the metal complexes are more effective than ligands. Furthermore, molecular docking simulation was used to obtain the energetic and binding sites for the interaction of the complexes with Mycobacterium tuberculosis enoyl-acyl carrier protein reductase (InhA), and results showed that complex 1 has more binding energy.
A new series of drug complexes from sulfa was prepared using Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Pt(II) ions. The isolated complexes are deliberately illustrated using spectral, thermal and different theoretical tools. The bidentate mode of coordination is proposed with all complexes. The octahedral configuration is the main structural formula proposed except d 8 systems. Significant parameters derived from spectra were deducted to assert on the proposed configurations. XRD and TEM tools display a great conformity in-between for proposing the nano-crystallite sizes of all investigated compounds. Implementing Gaussian 09 program for structural formulas used to obtain the optimized forms. Applying DFT/ B3LYP method, the frontier energy gaps were calculated and other important theoretical parameters. Utilizing molecular docking by AutoDock tools used to explain the experimental behavior of organic compounds toward the microorganisms from theoretical visualization. The docked complexes for 4ynu, 4d7h, 1zap, 1ecl, 3e5a, 1y0k and 1bqb protein receptors were investigated and the different energies were calculated. Pt(II), Zn(II) and Cu(II) complexes display significant inhibition for all microorganisms used in biological investigation. Moreover, the IC 50 calculated represent the distinguish priority of Ni(II) and Co(II) complexes in overcoming liver cancer.
Bulletin of The Chemical Society of Ethiopia, 2023
The azo ligand obtained from the diazotization reaction of 2-aminobenzothiazole and 4nitroaniline yielded a novel series of complexes with Co(II), Ni(II), Cu(II), and Zn(II) ions. The complexes were investigated using spectral techniques such as UV-Vis, FT-IR, 1 H and 13 C NMR spectroscopic analyses, LC-MS and atomic absorption spectrometry, electrical conductivity, and magnetic susceptibility. The molar ratio of the synthesized compounds was determined using the ligand exchange ratio, which revealed the metal-ligand ratios in the isolated complexes were 1:2. The synthesized complexes were tested for antimicrobial activity against S. aureus, E. coli, C. albicans, and C. tropicalis bacterial species. Additionally, their binding affinities were predicted using molecular docking analysis, and their pharmacokinetic and drug-likeness properties were evaluated.