Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Ghofrane Lahmadi
,
Mabrouk Horchani
,
Amal Dbeibia
,
Abdelkarim Mahdhi
ORCID logo ,
Anis Romdhane
,
Ata Martin Lawson
ORCID logo ,
Adam Daïch
,
Abdel Halim Harrath
ORCID logo ,
Hichem Ben Jannet
* ORCID logo ,
And Mohamed Othman
* ORCID logo
Version 1 : Received: 20 May 2023 / Approved: 23 May 2023 / Online: 23 May 2023 (03:33:09 CEST)

A peer-reviewed article of this Preprint also exists.

Lahmadi, G.; Horchani, M.; Dbeibia, A.; Mahdhi, A.; Romdhane, A.; Lawson, A.M.; Daïch, A.; Harrath, A.H.; Ben Jannet, H.; Othman, M. Novel Oleanolic Acid-Phtalimidines Tethered 1,2,3 Triazole Hybrids as Promising Antibacterial Agents: Design, Synthesis, In Vitro Experiments and In Silico Docking Studies. Molecules 2023, 28, 4655. Lahmadi, G.; Horchani, M.; Dbeibia, A.; Mahdhi, A.; Romdhane, A.; Lawson, A.M.; Daïch, A.; Harrath, A.H.; Ben Jannet, H.; Othman, M. Novel Oleanolic Acid-Phtalimidines Tethered 1,2,3 Triazole Hybrids as Promising Antibacterial Agents: Design, Synthesis, In Vitro Experiments and In Silico Docking Studies. Molecules 2023, 28, 4655.

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.

Keywords

Oleanolic acid; phtalimidines; triazole; click chemistry; antibacterial activity; molecular docking

Subject

Chemistry and Materials Science, Organic Chemistry

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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