title: Pentacyclic triterpene derivatives possessing polyhydroxyl ring A inhibit gram-positive bacteria growth by regulating metabolism and virulence genes expression.
abstract: The hydroxyl group in ring A of pentacyclic triterpene is essential for antibacterial activity. Pentacyclic triterpenes bearing three hydroxyl groups in ring A were mainly found in plants and displayed significant antibacterial activity. However, no study reported how to obtain this type of compounds by chemical modification. In this study, twenty-five new pentacyclic triterpenes bearing polyhydroxyl ring A were synthesized from parental compounds ursolic acid (UA) and oleanolic acid (OA). Here, we showed that most of these derivatives displayed a significantly increased activity against Gram-positive bacteria compared to parental compounds in vitro. Some of these compounds exhibited minimum inhibitory concentration values of 1-3-fold more potent than the positive controls. The structure-activity relationship studies demonstrated that introducing two hydroxyl groups at positions C-1 and C-2 together with a small alkyl ester group at C-17 of UA and OA strongly enhanced growth-inhibiting activity against Gram-positive bacteria. The antibacterial mechanism of the active derivatives was shown to be involved in regulating the expression of genes associated with peptidoglycan and respiratory metabolisms, as well as virulence factor in bacteria. The enhanced potency and unique mechanism of action of these new pentacyclic triterpenes make them a promising antibacterial agent for further studies.
authors: Ministry of Education Key Laboratory of Green Pesticide and Ago-Bioengineering, Center for Research and Development of Fine Chemicals of Guizhou University, Guiyang 550025, China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, China.
authors: Lirong
authors: L
authors: Huang
authors: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, China.
authors: Heng
authors: H
authors: Luo
authors: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, China.
authors: Qiji
authors: Q
authors: Li
authors: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, China.
authors: Daoping
authors: D
authors: Wang
authors: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, China.
authors: Jianxin
authors: J
authors: Zhang
authors: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, China. Electronic address: haoxj@mail.kib.ac.cn.
authors: Xiaojiang
authors: X
authors: Hao
authors: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, China. Electronic address: gzcnp@sina.cn.
authors: Xiaosheng
authors: X
authors: Yang
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D053978:Pentacyclic Triterpenes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D014774:Virulence / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D053978:Pentacyclic Triterpenes; D012333:RNA, Messenger
keywords: Antibacterial activity; Mechanism; Pentacyclic triterpene derivatives; Polyhydroxyl ring A; Synthesis