Synthesis, Spectroscopic Characterization, Antibacterial Activity, and Computational Studies of Novel Pyridazinone Derivatives (original) (raw)
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A new series of antibacterial pyrazolo-triazolo-pyrimidine derivatives 3a-3i were synthesized in two steps starting from aminopyrazole 1 and characterized by 1 H NMR 13 C NMR and HRES-MS. Their molecular geometry are also calculated by the Density Functional Theory (DFT) employing B3LYP level with 6-311G (d,p) basis set. All the synthesized compounds were tested for in vitro antibacterial activity against a panel of selected bacterial strains, by application of the Disc-Diffusion and MIC assays, using gentamicin as standard. The interactions of these compounds with the bacteria Pseudomonas aeruginosa (LasR) were performed by molecular docking studies.
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Heterocyclic compounds, including pyrimidine derivatives, exhibit a broad variety of biological and pharmacological activities. In this paper, a previously synthesized novel pyrimidine molecule is proposed, and its pharmaceutical properties are investigated. Computational techniques such as the density functional theory, ADMET evaluation, and molecular docking were applied to elucidate the chemical nature, drug likeness and antibacterial function of molecule. The viewpoint of quantum chemical computations revealed that the molecule was relatively stable and has a high electrophilic nature. The contour maps of HOMO-LUMO and molecular electrostatic potential were analyzed to illustrate the charge density distributions that could be associated with the biological activity. Natural bond orbital (NBO) analysis revealed details about the interaction between donor and acceptor within the bond. Drug likeness and ADMET analysis showed that the molecule possesses the agents of safety and the ...
Organic communications, 2022
Pyrimido[4,5-d]pyrimidine conveys antimicrobial activity against various micro pathogens having functionalized properties. As a result, this study has designed to illustrate the antibacterial, antifungal, and antiviral properties of pyrimido[4,5-d]pyrimidine. First of all, these structures have been optimized from the characterization of synthesis for calculating chemical descriptors by DFT. Next, the auto docking and target docking against 12 proteins, such as Pseudomonas aeruginosa (2Y0H), Bacillus cereus (1AH7), Escherichia coli (6DR3), Shigella dysenteriae (3FHH) Salmonella typhi (3FHU), Aspergillus niger (1ACZ), Aspergillus flavus (1XY3), Rhizomucor miehei (4WTP), Candida auris (6U8J), three proteins of SARS-CoV-2 (7T9J, 7T9L, and 7TB4) were performed for the determination of binding sites and binding affinity. One FDA approved drug (Ampicillin) has docked against 12 proteins while the Bacillus cereus (Bacteria), Aspergillus flavus (Fungus), and SARS-CoV-2, 7T9L (Omicron) are obtained the best binding affinity after docking. The most common residues are the PHE-66, ARG-176 and VAL-124 for Bacillus cereus, Aspergillus flavus and SARS-CoV-2, Omicron (7T9L), respectively, as they blocked the active sites by the ligands as inhibitors. It is revealed that this study contained both auto docking and target docking whereas the binding affinity of auto docking is that the binding affinity for auto docking is higher than target docking. Finally, among the nine compounds, three compounds show outstanding results against bacteria, fungus and virus. At last, molecular dynamics were performed to check the stability and validation of the docked complex and quantum calculations obtained the molecular properties, as well as ADMET, pharmacokinetics, Lipinski Rule and QSAR data.
Heliyon, 2021
Quantum chemical calculation, performance of selective antimicrobial activity using molecular docking analysis, RDG and experimental (FT-IR, FT-Raman) investigation of 4-[{2-[3-(4-chlorophenyl)-5-(4-propan-2-yl) phenyl)-4, 5-dihydro-1H-pyrazol-1-yl]-4-oxo-1, 3-thiazol-5(4H)-ylidene} methyl] benzonitrile
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A new class of β-lactam pharmacophore series of 2-Bromo-N-[4-(2-{[2-(substituted phenyl)-3-chloro-4-oxoazetidin-1-yl] amino}-2-oxoethyl) phenyl] pyridine-4carboxamide derivatives were designed, prepared, and screened for their antimycobacterial activities. The hydrazone derivatives were first synthesized via conventional and microwave methods, and then the β-lactam ring could be constructed via a [2+2] ketenimine cycloaddition. The structure of all synthesized compounds was characterized by FTIR, 1 H NMR, 13 C NMR, and Mass spectroscopy techniques. All the newly synthesized derivatives were found to be effective in inhibiting M. tuberculosis H37RV strain infection at concentrations of 12.5, 25.0, and 50.0 µg/mL using the MABA method. Amongst, the compound (6e) was found to be good potent antitubercular activity at 12.5 mg/mL concentration in comparison with the rest of the compounds using the standard therapeutic agent Streptomycin. Molecular dynamics simulation studies and Molecular docking studies have been performed against mycobacterial InhA enzyme to gain an insight into the possible mechanistic action in search of good potent antitubercular candidates.
Turkish Journal of Pharmaceutical Sciences, 2011
In the present study, six new derivatives of PYridazinone were synthesized and evaluate their anti-bacterial activity. The experimental work involves the synthesis of benzoyl propionic acid (a), then 6-phenyl-2,3,4,5-tetrahydro pyridazin-3-one (b) which was then condensed with various, aldehydes to form respective derivatives, AH the synthesized compounds were identified by IR, 1HNMR and antimicrobial activity was performed on the compounds synthesized against Staphylococcus aureus (MTCC 737), Staphylococcus epidermidis (MTCC 3615), Pseudomonas aeruginosa (MTCC 424) and Escherichia coli (MTCC 1687)
Chemical Biology & Drug Design, 2019
A library of novel pyrazole-imidazo[1,2-α]pyridine scaffolds was designed and synthesized through a one-pot three-component tandem reaction. The structures of synthesized conjugates were confirmed by spectroscopic techniques (NMR, IR and HRMS). In vitro antibacterial evaluation of the twelve synthesized molecules (7a, 8a-k) against methicillin-resistant Staphylococcus aureus and normal strains of Escherichia coli, Salmonella typhimurium, Klebsiella pneumonia and Pseudomonas aeruginosa established 8b, 8d, 8e, 8h and 8i as potent antibacterial agents with superior minimum bactericidal concentration, compared with standard drug ciprofloxacin. Molecular docking studies of all active compounds into the binding site of glucosamine-6-phosphate synthase were further performed in order to have a comprehensive understanding of putative binding modes within the active sites of the receptor. K E Y W O R D S antibacterial, imidazo[1,2-α]pyridine, molecular docking, pyrazole, tandem reaction 2 | EBENEZER Et al.
Synthesis, antibacterial and antifungal activity of some new pyridazinone metal complexes
European Journal of Medicinal Chemistry, 2006
The new various metal complexes of 5-benzoyl-4-hydroxy-2-methyl-6-phenyl-2H-pyridazin-3-one were synthesized. All the complexes were evaluated for their antimicrobial activities against Gram-positive, Gram-negative bacteria and fungi using microdilution procedure. The Cd(II) and Ni(II) complexes exhibited selective and effective activities against one Gram-positive bacterium (Staphylococcus aureus ATCC 6538), one Gram-negative bacterium (Pseudomonas putida ATCC 12633) and against two yeast (Candida albicans ATCC 27541 and Candida tropicalis 1828) in contrast to poor activity observed other microorganisms. The new synthesized complexes were characterized using IR, 1 H-NMR and UV spectral data together with elemental analysis.
Letters in Drug Design & Discovery, 2020
Background: Antimicrobial Resistance (AMR) and Tuberculosis (TB) are global concern. According to the WHO fact sheet on tuberculosis, in 2017, 10 million people fell ill with TB, and 1.6 million including 230,000 children died from the disease. There is a critical need of design and development of novel chemotherapeutic agents to combat the emergence and increasing prevalence of resistant pathogens. In the present study, a new series of 1,3,4-oxadiazoles incorporating benzimidazole and pyridine scaffolds in a single molecular framework has been reported. Methods: The structures of the synthesized derivatives (4a to 4e) were assigned by IR, NMR and mass spectral techniques. The hybrid compounds were evaluated for their antimicrobial, antitubercular and antioxidant activities. In addition, docking simulations were performed to study ligand-protein interactions and to determine the probable binding conformations. Results: Molecule 4a has shown anti-tubular activities with MIC 1.6 μg/ml. As compared to ascorbic acid activities (IC 50 = 62.91 µg/ml), molecule 4e exhibited better antioxidant activities (IC 50 = 24.85 µg/ml). Also, molecule 4e has shown significant antimicrobial activities. Conclusion: The synthesized derivatives from 4a to 4e have exhibited various medicinal activities and could be emerged as lead compounds and further explored as potential therapeutic agents.