Multi-layered antimicrobial synergism of (E)-caryophyllene with minor compounds, tecleanatalensine B and normelicopine, from the leaves of Vepris gossweileri (I. Verd.) Mziray

Abstract

An aromatic alkaloid-rich ‘absolute’ extract from Vepris gossweileri inhibited Saccharomyces cerevisiae at 62.5 μg.mL⁻¹ and Bacillus subtilis at 500 μg.mL⁻¹_. A loss of activity upon fractionation indicated possible synergistic effects. Three new acridones, gossweicridone A (3), B (4) and C (5) and known compounds from the extract were inactive. Combinations of compounds showed that a sub-fraction containing mixtures of minor compounds with (Ε)-caryophyllene augmented activity by 50-folds, with MIC values of 19.6 μg.mL⁻¹ for S. cerevisiae and 375.0 μg.mL⁻¹ for B. subtilis, demonstrating potent ΣFIC values of 0.02 and 0.375 respectively. From the active sub-fraction, three compounds were assigned as tecleanatalensine B, 13S-hydroxy-9Z,11E,15E-octadecatrienoic acid and normelicopine. In combination with (Ε)-caryophyllene they separately demonstrated MIC values of 18 μg.mL⁻¹, 34 μg.mL⁻¹ and 16 μg.mL⁻¹_, respectively against S. cerevisiae. The synergistic combinations were more potent with addition of pheophytin A, suggesting that the synergistic antifungal effect of the extract is multi-layered.

Graphical Abstract

Keywords:

• Vepris gossweileri (I. Verd.) Mziray
• acridone
• furoquinoline
• Saccharomyces cerevisiae strain BY4743
• synergism and potentiation
• antimicrobial effects

Acknowledgements

The authors thank Sarah Redstone and colleagues in the Quarantine House RBG, Kew for initially growing the plant material from seed, and Bradley Gangadeen of the Science Glass for growing it on. Dr Emile Kami, former Head of the National Herbarium of Republic of Congo (IEC) is thanked for expediting authoristaion for botanical prospection and export of material to RBG, Kew. Aydrif Laurel Mpandzou assisted collecting the material in Congo. Paul Reed, John Merry and Colin Harris of MPD Congo S.A. provided logistic support.

Disclosure statement

The authors declare no competing financial interest.