Novel Oleanolic Acid-Phtalimidines Tethered 1,2,3 Triazole Hybrids as Promising Antibacterial Agents: Design, Synthesis, In Vitro Experiments and In Silico Docking Studies

• Published in: Molecules (Basel, Switzerland) Switzerland), 2023-06, Vol.28 (12), p.4655
• Main Authors: Lahmadi, Ghofrane, Horchani, Mabrouk, Dbeibia, Amal, Mahdhi, Abdelkarim, Romdhane, Anis, Lawson, Ata Martin, Daïch, Adam, Harrath, Abdel Halim, Ben Jannet, Hichem, Othman, Mohamed
• Format: Article
• Language: English
• Subjects: Acids; Agricultural production; Agricultural wastes; Anti-Bacterial Agents - chemistry; Antibacterial activity; Antibacterial agents; Antibiotics; Bacteria; Bioactive compounds; Cancer; click chemistry; Design; Gram-negative bacteria; Gram-positive bacteria; Hybrids; Hydrogen; Hydrogen bonding; Hydrophobicity; Listeria monocytogenes; Microbial Sensitivity Tests; Molecular docking; Molecular Docking Simulation; Molecular Structure; Olea europaea; Oleanolic acid; Oleanolic Acid - pharmacology; phtalimidines; Protein binding; Proteins; Pseudomonas aeruginosa; Salmonella Typhimurium; Staphylococcus aureus; Structure-Activity Relationship; Tetracycline; Tetracyclines; triazole; Triazoles; Triazoles - chemistry; Triazoles - pharmacology
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28124655

As part of the valorization of agricultural waste into bioactive compounds, a series of structurally novel oleanolic acid ((3β-hydroxyolean-12-en-28-oic acid, )-phtalimidines (isoindolinones) conjugates - bearing 1,2,3-triazole moieties were designed and synthesized by treating an azide previously prepared from isolated from olive pomace ( L.) with a wide range of propargylated phtalimidines using the Cu(I)-catalyzed click chemistry approach. and its newly prepared analogues, - were screened in vitro for their antibacterial activity against two Gram-positive bacteria, and , and two Gram-negative bacteria, and . Attractive results were obtained, notably against . Compounds , , and exhibited the highest antibacterial activity when compared with and other compounds in the series against tested pathogenic bacterial strains. A molecular docking study was performed to explore the binding mode of the most active derivatives into the active site of the ABC substrate-binding protein Lmo0181 from . Results showed the importance of both hydrogen bonding and hydrophobic interactions with the target protein and are in favor of the experimental data.