Synthesis, antimicrobial activity and molecular docking study of benzyl functionalized benzimidazole silver(I) complexes.

In this study, a series of N-functionalized benzimidazole silver(I) complexes were prepared and characterized by FT-IR, 1H, 13C{1H} NMR spectroscopy, and elemental analysis. Synthesized N-benzylbenzimidazole silver(I) complexes were evaluated for their antimicrobial activities against bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and the fungal strains Candida albicans and Candida glabrata. The results indicated that N-alkylbenzimidazole silver(I) complexes exhibited good antimicrobial activity compared to N-alkylbenzimidazole derivatives. Especially, complex 2e presented perfect antimicrobial activity than the other complexes. The characterized molecules were optimized by DFT-based calculation methods and the optimized molecules were analyzed in detail by molecular docking methods against bacterial DNA-gyrase and CYP51. The amino acid residues detected for both target molecules are consistent with expectations, and the calculated binding affinities and inhibition constants are promising for further studies. A series of N-alkylbenzimidazole silver(I) complexes were synthesized and fully characterized by means of 1H NMR, 13C NMR, and FT-IR spectroscopies. Synthesized N-alkylbenzimidazole silver(I) complexes were investigated for their antimicrobial activities against bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and the fungal strains Candida albicans and Candida glabrata. All complexes showed better activity according to Ampicilin against Pseudomonas aeruginosa. The molecules which were firstly optimized by DFT-based calculation methods were also analyzed by molecular docking methods against DNA gyrase of E. Coli and CYP51. 338 × 190 mm (96 × 96 DPI).

Design, synthesis, antimicrobial activity and molecular docking study of cationic bis-benzimidazole-silver(I) complexes.

Two series of bis(1-alkylbenzimidazole)silver(I) nitrate and bis(1-alkyl-5,6-dimethylbenzimidazole)silver(I) nitrate complexes, in which the alkyl substituent is either an allyl, a 2-methylallyl, an isopropyl or a 3-methyloxetan-3-yl-methyl chain, were synthesized and fully characterized. The eight N-coordinated silver(I) complexes were screened for both antimicrobial activities against Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii) and Gram-positive (Staphylococcus aureus, Staphylococcus aureus MRSA, and Enterococcus faecalis) bacteria and antifungal activities against Candida albicans and Candida glabrata strains. Moderate minimal inhibitory concentrations (MIC) of 0.087 µmol/mL were found when the Gram-negative and Gram-positive bacteria were treated with the silver complexes. Nevertheless, MIC values of 0.011 µmol/mL, twice lower than for the well-known fluconazole, against the two fungi were measured. In addition, molecular docking was carried out with the structure of Escherichia coli DNA gyrase and CYP51 from the pathogen Candida glabrata with the eight organometallic complexes, and molecular reactivity descriptors were calculated with the density functional theory-based calculation methods.

An efficient new method of ytterbium(III) triflate catalysis approach to the synthesis of substituted pyrroles: DFT, ADMET, and molecular docking investigations.

In this study, the one-pot synthetic methodology for the preparation of substituted pyrroles with diethyl acetylene-dicarboxylate is reported for the various pyrrole derivatives via the Trifimow synthesis process from oximes. This method also offers the literature as a cyclization pathway using a ytterbium triflate catalyst. Another importance of this study is the use of pyrrole derivatives in pharmaceuticals, biological processes, and agrochemicals. From this point of view, the development of a new catalyst in synthetic organic chemistry and the difference in the method is also important. The syntheses of the target substituted pyrroles are accomplished in high yields. Also, all synthesized structures were confirmed by 1H NMR, 13C NMR, and IR spectra. The DFT computations were leveraged for structural and spectroscopic validation of the compounds. Then, FMO and NBO analyses were subsequently employed to elucidate the reactivity characteristics and intramolecular interactions within these compounds. Also, ADMET indices were ascertained to assess potential pharmacokinetic properties, drug-like qualities, and possible adverse effects of these compounds. Last, optimized molecules were analyzed by molecular docking methods against crystal structures of Bovine Serum Albumin and Leukemia Inhibitory Factor, and their binding affinities, interaction details, and inhibition constants were determined.

Strychnos alkaloids: total synthesis, characterization, DFT investigations, and molecular docking with AChE, BuChE, and HSA.

An efficient five steps, the protection-deprotection synthetic a novel synthetic routes to(±) noruleine (±)-uleine, are reported starting from tetrahydrocarbazole fused monoalkyl nitrile at C-2 position that is prepared on multigram scale from 2-(3-ethyl-1-oxo-2,3,4,9-tetrahydro-1H-carbazol-2-yl)acetonitrile (1) as well as the key azocino[4,3-b]indole skeleton is constructed via the tetrafluoro-1,4-benzoquinone (TFB)-mediated cyclization of a tetrahydrocarbazole derivative possessing direct amide synthesis from nitrile. As a result, Total synthesis of noruleine and uleine has been developed, which is accomplished in 4 and 5- steps synthesis of the ABCD tetracyclic of the strychnos alkaloids with an overall yield of 44% and 39%, respectively. The DFT computations were performed with B3LYP/6-311g(d,p) level to determine inter and intramolecular interactions and reactivity features of the compound 3-6. Also, TD-DFT computations were performed to characterize the electronic absorption spectra of all compounds. Last, the interactions of compounds 3-6 with selected targets AChE, BuChE, and HSA were evaluated in light of the molecular dockings. The bioactivity and drug-likeness scores revealed that compound 6 3-6 can be proper candidate for future drug-design studies more than the other compounds.

Silver(I) Complexes Based on Oxadiazole-Functionalized α-Aminophosphonate: Synthesis, Structural Study, and Biological Activities.

Two silver(I) complexes, bis{diethyl[(5-phenyl-1,3,4-oxadiazol-2-yl-κN3:κN4-amino) (4-trifluoromethylphenyl)methyl]phosphonate-(tetrafluoroborato-κF)}-di-silver(I) and tetrakis-{diethyl[(5-phenyl-1,3,4-oxadiazol-2-yl-κN3-amino)(4-trifluoromethylphenyl)methyl]phosphonate} silver(I) tetrafluoroborate, were prepared starting from the diethyl[(5-phenyl-1,3,4-oxadiazol-2-yl-amino)(4-trifluoromethylphenyl)methyl]phosphonate (1) ligand and AgBF4 salt in Ag/ligand ratios of 1/1 and 1/4, respectively. The structure, stoichiometry, and geometry of the silver complexes were fully characterized by elemental analyses, infrared, single-crystal X-ray diffraction studies, multinuclear NMR, and mass spectroscopies. The binuclear complex ([Ag2(1)2(BF4)2]; 2) crystallizes in the monoclinic asymmetric space group P21/c and contains two silver atoms adopting a {AgN2F} planar trigonal geometry, which are simultaneously bridged by two oxadiazole rings of two ligands, while the mononuclear complex ([Ag(1)4]BF4; 3) crystallizes in the non-usual cubic space group Fd-3c in which the silver atom binds to four distinct electronically enriched nitrogen atoms of the oxadiazole ring, in a slightly distorted {AgN4} tetrahedral geometry. The α-aminophosphonate and the monomeric silver complex were evaluated in vitro against MCF-7 and PANC-1 cell lines. The silver complex is promising as a drug candidate for breast cancer and the pancreatic duct with half-maximal inhibitory concentration (IC50) values of 8.3 ± 1.0 and 14.4 ± 0.6 µM, respectively. Additionally, the interactions of the ligand and the mononuclear complex with Vascular Endothelial Growth Factor Receptor-2 and DNA were evaluated by molecular docking methods.

Cyanopropyl functionalized benzimidazolium salts and their silver N-heterocyclic carbene complexes: Synthesis, antimicrobial activity, and theoretical analysis.

The reaction of N-substituted benzimidazole with 4-bromobutyronitrile gives the corresponding benzimidazolium salts as N-heterocyclic carbene (NHC) precursors. Silver(I) carbene complexes are synthesized by the reaction of the corresponding benzimidazolium salts with Ag2 O in dichloromethane. These new NHC precursors and Ag-NHC complexes were characterized by spectroscopy techniques and also screened for their antibacterial activities against the standard bacterial strains Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Enterococcus faecalis, and the standard fungal strains Candida albicans and Candida glabrata, and promising results were achieved. The compounds were also analyzed by density functional theory (DFT)/time-dependent DFT and docking methods.

Novel Ag(I)-NHC complex: synthesis, in vitro cytotoxic activity, molecular docking, and quantum chemical studies.

The importance of organometallic complexes in cancer biology has attracted attention in recent years. In this paper, we look for the in vitro cytotoxic capability of novel benzimidazole-based N-heterocyclic carbene (NHC) precursor (1) and its Ag(I)-NHC complex (2). For this purpose, these novel Ag(I)-NHC complex (2) was characterized by spectroscopic techniques (1H, 13C{1H} nuclear magnetic resonance (NMR), and Fourier-transform infrared spectroscopy (FT-IR)). Then, in vitro cytotoxic activities of NHC precursor (1) and Ag(I)-NHC complex (2) were investigated against MCF-7, MDA-MB-231 human breast, DU-145 prostate cancer cells, and L-929 healthy cells using MTT assay for 24, 48, and 72 h incubation times. Ag(I)-NHC complex (2) showed promising in vitro cytotoxic activity against all cell lines for three incubation times, with IC50 values lower than 5 µM. It was also determined that (NHC) precursor (1) were lower in vitro cytotoxic activity than Ag(I)-NHC complex (2) against all cell lines. Selectivity indexes (SIs) of Ag(I)-NHC complex (2) against cancer cells were found higher than 2 for 24 and 48 h incubation time. Besides, the electronic structure and spectroscopic data of the newly synthesized precursor and its Ag-complex have been supported by density functional theory (DFT) calculations and molecular docking analysis. After, the anticancer activity of these compounds has been discussed considering the results of the frontier molecular orbital analysis. We hope that the obtained results from the experiments and computational tools will bring a new perspective to cancer research in terms of supported by quantum chemical calculations.

Synthesis of Novel 1,3,4-Oxadiazole-Derived α-Aminophosphonates/α-Aminophosphonic Acids and Evaluation of Their In Vitro Antiviral Activity against the Avian Coronavirus Infectious Bronchitis Virus.

An efficient and simple approach has been developed for the synthesis of eight dialkyl/aryl[(5-phenyl-1,3,4-oxadiazol-2-ylamino)(aryl)methyl]phosphonates through the Pudovik-type reaction of dialkyl/arylphosphite with imines, obtained from 5-phenyl-1,3,4-oxadiazol-2-amine and aromatic aldehydes, under microwave irradiation. Five of them were hydrolyzed to lead to the corresponding phosphonic acids. Selected synthesized compounds were screened for their in vitro antiviral activity against the avian bronchitis virus (IBV). In the MTT cytotoxicity assay, the dose-response curve showed that all test compounds were safe in the range concentration of 540-1599 µM. The direct contact of novel synthesized compounds with IBV showed that the diethyl[(5-phenyl-1,3,4-oxadiazol-2-ylamino)(4-trifluoromethoxyphenyl)methyl]phosphonate (5f) (at 33 µM) and the [(5-phenyl-1,3,4-oxadiazol-2-ylamino)(4-trifluoromethylphenyl)methyl] phosphonic acid (6a) (at 1.23 µM) strongly inhibited the IBV infectivity, indicating their high virucidal activity. However, virus titers from IBV-infected Vero cells remained unchanged in response to treatment with the lowest non-cytotoxic concentrations of synthesized compounds suggesting their incapacity to inhibit the virus replication inside the host cell. Lack of antiviral activity might presumably be ascribed to their polarity that hampers their diffusion across the lipophilic cytoplasmic membrane. Therefore, the interactions of 5f and 6a were analyzed against the main coronavirus protease, papain-like protease, and nucleocapsid protein by molecular docking methods. Nevertheless, the novel 1,3,4-oxadiazole-based α-aminophosphonic acids and α-amino-phosphonates hold potential for developing new hygienic virucidal products for domestic, chemical, and medical uses.

Synthesis, characterization, antimicrobial and antibiofilm activity, and molecular docking analysis of NHC precursors and their Ag-NHC complexes.

Microorganisms attach to surfaces and interfaces and form biofilms which create a sheltered area for host cell response. Therefore, biofilms provide troubles in fields such as medicine, food, and pharmaceuticals. Inhibition of formation of biofilms through hindering of quorum sensing could be a method for the production of new generation antibiotics. In this study, four new benzimidazole type NHC precursors (1-allyl-3-benzyl-5,6-dimethylbenzimidazolium chloride, 1-allyl-3-(2,4,6-trimethylbenzyl)-5,6-dimethylbenzimidazolium chloride, 1-allyl-3-(2,3,5,6-tetramethylbenzyl)-5,6-dimethylbenzimidazolium chloride, and 1-allyl-3-(2,3,4,5,6-pentamethylbenzyl)-5,6-dimethylbenzimidazolium chloride and Ag-NHC complexes of these molecules were synthesized and characterized by elemental analysis, FT-IR spectroscopy, 1H, and 13C{1H} NMR spectroscopy, LC-MS, and single crystal crystallography. Antimicrobial and biofilm formation inhibition activities of the molecules were evaluated. In addition, the activities of the molecules were examined in detail by molecular docking analysis. According to the results obtained, higher activity was achieved with the complex molecules when compared with the benzimidazole derivative ligands.

PEPPSI complexes as potential prodrugs: enzyme inhibition, antioxidant activity, electrochemical characterization, molecular docking analysis.

In this study, enzyme inhibition and antioxidant activity analyzes of previously characterized pyridine-enhanced precatalyst preparation stabilization and initiation (PEPPSI)-type Palladium(II) complexes with benzimidazole-type ligands {dichloro[L]pyridine palladium(II), L1: 1-(2-methyl-2-propenyl)-3-[benzylbenzimidazole]-2-ylidene, L2: 1-(2-methyl-2-propenyl)-3-[4-chloro benzylbenzimidazole]-2-ylidene, L3: 1-(2-methyl-2-propenyl)-3-[3-methylbenzylbenzimidazole]-2-ylidene, L4: 1-(2-methyl-2-propenyl)-3-[3,4,5-thrimethoxybenzylbenzimidazole]-2-ylidene, L5: 1-(2-methyl-2-propenyl)-3-[3-naphthylbenzylbenzimidazole]-2-ylidene, L6: 1-(2-methyl-2-propenyl)-3-[anthracen-9-ylmethylbenzimidazole]-2-ylidene} were performed and evaluated as potential drugs for neurodegenerative disorders such as Alzheimer disease and Parkinson disease. Inhibition of tyrosinase enzyme of N-heterocyclic carbenes (NHC) complexes was determined for the first time in literature. Chelating activities of the complexes were determined and compared with EDTA. Electrochemical characterization was performed using cyclic voltammetry method. Moreover, global reactivity descriptors and electronic transitions were evaluated by DFT/TDDFT methods and molecular docking interactions with human acetylcholine esterase, human butyrylcholine esterase and oxidoreductase were studied.