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

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, OA-1 )-phtalimidines (isoindolinones) conjugates 18a - u bearing 1,2,3-triazole moieties were designed and synthesized by treating an azide 4 previously prepared from OA-1 isolated from olive pomace ( Olea europaea L.) with a wide range of propargylated phtalimidines using the Cu(I)-catalyzed click chemistry approach. OA-1 and its newly prepared analogues, 18a - u, were screened in vitro for their antibacterial activity against two Gram-positive bacteria, Staphylococcus aureus and Listeria monocytogenes , and two Gram-negative bacteria, Salmonella thyphimurium and Pseudomonas aeruginosa . Attractive results were obtained, notably against L. monocytogenes . Compounds 18d , 18g , and 18h exhibited the highest antibacterial activity when compared with OA-1 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 L. monocytogenes . Results showed the importance of both hydrogen bonding and hydrophobic interactions with the target protein and are in favor of the experimental data.