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Synthesis and Biological Evaluation of Pentacyclic Triterpenoid Derivatives as Potential Novel Antibacterial Agents

Wu, Panpan, Tu, Borong, Liang, Jinfeng, Guo, Shengzhu, Cao, Nana, Chen, Silin, Luo, Zhujun, Li, Jiahao, Zheng, Wende, Tang, Xiaowen, Li, Dongli, Xu, Xuetao, Liu, Wenfeng, Zheng, Xi, Sheng, Zhaojun, Roberts, Adam ORCID: https://orcid.org/0000-0002-0760-3088, Zhang, Kun and Hong, Weiqian David (2021) 'Synthesis and Biological Evaluation of Pentacyclic Triterpenoid Derivatives as Potential Novel Antibacterial Agents'. Bioorganic Chemistry, Vol 109, Issue 104692.

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Abstract

A series of ursolic acid (UA), oleanolic acid (OA) and 18β-glycyrrhetinic acid (GA) derivatives were synthesized by introducing a range of substituted aromatic side-chains at the C-2 position after the hydroxyl group at C-3 position was oxidized. Their antibacterial activities were evaluated in vitro against a panel of four Staphylococcus strains. The results revealed that the introduction of aromatic side-chains at the C-2 position of GA led to the discovery of potent triterpenoid derivatives for inhibition of both drug sensitive and resistant S. aureus, while the other two series derivatives of UA and OA showed no significant antibacterial activity even at high concentrations. In particular, GA derivative showed good potency against all four strains of Staphylococcus (MIC = 1.25 - 5 μmol/L) with acceptable pharmacokinetics properties and low cytotoxicity in vitro. Molecular docking was also performed using S. aureus DNA gyrase structure to rationalize the observed antibacterial activity. Therefore, this series of GA derivatives have strong potential for the development of a new type of triterpenoid antibacterial agent.

Item Type: Article
Subjects: QV Pharmacology > Anti-Bacterial Agents. Tissue Extracts > QV 350 Anti-bacterial agents (General or not elsewhere classified)
QV Pharmacology > QV 38 Drug action.
QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified.
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1016/j.bioorg.2021.104692
Depositing User: Cathy Waldron
Date Deposited: 10 Feb 2021 18:57
Last Modified: 24 Feb 2021 12:18
URI: https://archive.lstmed.ac.uk/id/eprint/16760

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