Multi-layered antimicrobial synergism of (<i>E</i>)-caryophyllene with minor compounds, tecleanatalensine B and normelicopine, from the leaves of <i>Vepris gossweileri</i> (I. Verd.) Mziray
Moses K. Langat, Yisau Mayowa, Nicholas J. Sadgrove, Mohammed Danyaal, Thomas A. K. Prescott, Teva Kami, Sianne Schwikkard, James Barker, Martin Cheek
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.