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

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 ╬úFIC 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.