Design, synthesis, nitric oxide release and antibacterial evaluation of novel nitrated ocotillol-type derivatives

Yi Bi, Xiao Yang, Tingting Zhang, Zeyun Liu, Xiaochen Zhang, Jing Lu, Keguang Cheng, Jinyi Xu, Hongbo Wang, Guangyao Lv, Peter John Lewis, Qingguo Meng, Cong Ma

Research output: Journal article publicationJournal articleAcademic researchpeer-review

21 Citations (Scopus)

Abstract

Abstract Nitric oxide (NO) and its auto-oxidation products are known to disrupt normal bacterial function and NO releasing molecules have the potential to be developed as antibacterial leads in drug discovery. We have designed and synthesized a series of novel nitrated compounds by combining NO releasing groups with ocotillol-type triterpenoids, which have previously demonstrated activity only against Gram-positive bacteria. The in vitro NO release capacity and antibacterial activity were sequentially evaluated and the data showed that most of the synthesized compounds could release nitric oxide. Compound 16a, 17a and 17c, with nitrated aliphatic esters at C-3 position, displayed higher NO release than other analogues, correlating to their good antibacterial activity, in which 17c demonstrated broad-spectrum activity against both Gram positive and -negative bacteria, as well as excellent synergism at sub-minimum inhibitory concentration when using with kanamycin and chloramphenicol. Furthermore, the epifluorescent microscopic study indicated that the ocotillol-type triterpenoid core may induce NO release on the bacterial membrane. Our results demonstrate that nitrated substitutions at C-3 of ocotillol-type derivatives could provide an approach to expand their antibacterial spectrum, and that ocotillol-type triterpenoids may also be developed as appropriate carriers for NO donors in antibacterial agent discovery with low cytotoxicity.
Original languageEnglish
Article number7948
Pages (from-to)71-80
Number of pages10
JournalEuropean Journal of Medicinal Chemistry
Volume101
DOIs
Publication statusPublished - 1 Jan 2015
Externally publishedYes

Keywords

  • Antibacterial activity
  • NO release
  • Ocotillol
  • Synergistic effect
  • Triterpenoid

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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