1. Discovery of potent natural product higenamine derivatives as novel Anti-Fusobacterium nucleatum agents.
- Author
-
Su S, Bu Q, Bai X, Huang Y, Wang F, Hong J, Fang JY, Wu S, and Sheng C
- Subjects
- Humans, Fusobacterium nucleatum, Anti-Bacterial Agents pharmacology, Colorectal Neoplasms
- Abstract
Fusobacterium nucleatum (F. nucleatum) is closely associated with the occurrence and development of colorectal cancer (CRC). Discovery of specific antibacterial agents against F. nucleatum was urgent for the prevention and treatment of CRC. We screened a natural product library and successfully identified higenamine as an antibacterial hit against F. nucleatum. Further hit optimizations led to the discovery of new higenamine derivatives with improved anti-F. nucleatum activity. Among them, compound 7c showed potent antibacterial activity against F. nucleatum (MIC
50 = 0.005 μM) with good selectivity toward intestinal bacteria and normal cells. It significantly inhibited the migration of CRC cells induced by F. nucleatum. Mechanism study revealed that compound 7c impaired the integrity of biofilm and cell wall, which represents a good starting point for the development of novel anti-F. nucleatum agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)- Published
- 2023
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