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

Abstract

As part of valorisation 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-v bearing 1,2,3-triazole moieties were designed and synthesized by treating a previously azide 4 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-v 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. Molecular docking study was performed to explore the binding mode of the most active derivatives against the target protein from L. monocytogenes. Results showed the importance of both hydrogen bonding and hydrophobic interactions with the target protein and are in favor to the experimental data.