Total syntheses and antibacterial evaluations of cudraflavones A-C and related Flavones

Hongbo Dong; Li Liao; Pei Yu; Bin Long; Yufei Che; Lan Lu; Bing Xu

doi:10.1016/j.bioorg.2023.106764

Total syntheses and antibacterial evaluations of cudraflavones A-C and related Flavones

Bioorg Chem. 2023 Nov:140:106764. doi: 10.1016/j.bioorg.2023.106764. Epub 2023 Aug 9.

Authors

Hongbo Dong¹, Li Liao¹, Pei Yu², Bin Long², Yufei Che², Lan Lu³, Bing Xu⁴

Affiliations

¹ Engineering Research Center for Pharmaceuticals and Equipment of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu 610106, PR China; Anti-infective Agent Creation Engineering Research Centre of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu 610106, PR China.
² Engineering Research Center for Pharmaceuticals and Equipment of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu 610106, PR China.
³ Anti-infective Agent Creation Engineering Research Centre of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu 610106, PR China.
⁴ Department of Pediatric Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, PR China. Electronic address: yourxubing@126.com.

PMID: 37573609
DOI: 10.1016/j.bioorg.2023.106764

Abstract

The total syntheses of the natural prenylated flavones cudraflavones A-C (1-3), artoheterophyllin D (28) and artelasticin (29) are reported, along with the evaluations of their antibacterial activities. The key steps of the synthesis involved a Baker-Venkataraman rearrangement and an intramolecular cyclization for the construction of the flavone core and the regioselective formation of the pyran and isopentenyl scaffolds. The tested natural flavones 1-3 and 27-29 exhibited potent activity against S. aureus ATCC 29213, S. epidermidis ATCC 14990, E. faecalis ATCC 29212 and B. subtilis ATCC 6633 with MIC values ranging from 0.125 μg/mL to 16 μg/mL. Compound 3 displayed the strongest potency, with MIC values in the range between 0.125 and 1 μg/mL, as a potential candidate to combat G⁺ bacterial infections. Preliminary mechanism of action studies suggested that this compound killed bacteria by disrupting bacterial membrane integrity.

Keywords: Antibacterial activity; Natural product; Prenylated flavone; Total synthesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology
Bacteria
Flavones* / pharmacology
Microbial Sensitivity Tests
Plant Extracts / pharmacology
Staphylococcus aureus*

Substances

Anti-Bacterial Agents
Flavones
Plant Extracts