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

Langat, Moses K., Mayowa, Yisau, Sadgrove, Nicholas, Danyaal, Mohammed, Prescott, Thomas A. K., Kami, Teva, Schwikkard, Sianne, Barker, James and Cheek, Martin (2021) Multi-layered antimicrobial synergism of (E)-caryophyllene with minor compounds, tecleanatalensine B and normelicopine, from the leaves of 'Vepris gossweileri' (I. Verd.) Mziray. Natural Product Research, ISSN (print) 1478-6419 (Epub Ahead of Print)

Abstract

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

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