Synthesis, Spectroscopic Characterization, Antibacterial Activity, and Computational Studies of Novel Pyridazinone Derivatives

• Published in: Molecules (Basel, Switzerland) Vol. 28; no. 2; p. 678
• Main Authors: Daoui, Said, Direkel, Şahin, Ibrahim, Munjed M, Tüzün, Burak, Chelfi, Tarik, Al-Ghorbani, Mohammed, Bouatia, Mustapha, Karbane, Miloud El, Doukkali, Anass, Benchat, Noureddine, Karrouchi, Khalid
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09-01-2023; MDPI
• Subjects: Acinetobacter baumannii; ADMET; Anti-Bacterial Agents - chemistry; antibacterial; Antibacterial activity; Antibiotics; Antimicrobial agents; Bacteria; Bacterial infections; Computer applications; Crystal structure; DFT; Drug resistance; E coli; Electrostatic properties; Escherichia coli; Gram-negative bacteria; Gram-positive bacteria; Methicillin; Microbial Sensitivity Tests; Molecular docking; Molecular Docking Simulation; Molecular orbitals; Molecular structure; NMR; Nuclear magnetic resonance; Pathogens; Pseudomonas aeruginosa; Pyridazinone; Salmonella Typhimurium; Spectroscopy, Fourier Transform Infrared; Staphylococcus aureus; Staphylococcus infections; synthesis; synthesis; antibacterial; DFT; molecular docking; ADMET; pyridazinone
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28020678

In this work, a novel series of pyridazinone derivatives (
-
) were synthesized and characterized by NMR (
H and
C), FT-IR spectroscopies, and ESI-MS methods. All synthesized compounds were screened for their antibacterial activities against
(Methicillin-resistant),
,
,
, and
. Among the series, compounds
and
were found to be active against
(MRSA),
, and
with the lowest MIC value range of 3.74-8.92 µM. Afterwards, DFT calculations of B3LYP/6-31++G(d,p) level were carried out to investigate geometry structures, frontier molecular orbital, molecular electrostatic potential maps, and gap energies of the synthesized compounds. In addition, the activities of these compounds against various bacterial proteins were compared with molecular-docking calculations. Finally, ADMET studies were performed to investigate the possibility of using of the target compounds as drugs.