Antiplasmodial leads in oleo-gum-resins from Burseraceae: bioactivity-guided fractionation of myrrh

Malaria is a life-threatening infectious disease caused by Plasmodium spec. that are transmitted to human blood by the bite of Anopheles mosquitoes. In the course of our continued search for antiprotozoal natural products, an alcoholic extract of Commiphora myrrha showed antiplasmodial activity in vitro [1]. Thus myrrh, the oleo-gum-resin exsuded by species of the genus Commiphora, was subjected to a systematic investigation. Antiplasmodial tests were conducted according to established protocols [2]. A dichloromethane extract showed an IC₅₀ value of 1.03 µg/mL in vitro against Plasmodium falciparum (NF54 strain). In a bioactivity-guided fractionation, several chromatographic separation steps resulted in the isolation of 12 sesquiterpenoids, 3 nortriterpenoids of the mansumbinane-type and one triterpene, 20-hydroxydammar-24-en-3,16-dione. Isolated compounds were characterized and identified by spectroscopic means and comparison to literature data. Among the sesquiterpenoids 3 compounds are, to the best of our knowledge, reported for the first time, namely, rel-(5S,6R,7aS)-6-((E)-2-methoxyvinyl)-3,6-dimethyl-5-(prop-1-en-2-yl)-5,6,7,7a-tetrahydrobenzofuran-2(4H)-one, rel-(5S,6R,7aR)-6-((E)-2-methoxyvinyl)-3,6-dimethyl-5-(prop-1-en-2-yl)-5,6,7,7a-tetrahydrobenzofuran-2(4H)-one and rel-(4aR,5S,7S,7aS)-7-methoxy-3,5,8-trimethyl-5,6,7,7a-tetrahydroazuleno[6,5-b]furan-4(4aH)-one. The dammarane triterpene showed the best antiplasmodial activity so far with an IC₅₀ value of 6.8µM. Further compounds are still under isolation and will also be tested.

This project is an activity within the Research Network Natural Products against Neglected Diseases (ResNet NPND; http://www.resnetnpnd.org/). HLG thanks Cusanuswerk for a doctoral scholarship.

[1] Llurba Montesino N et al. Molecules 2015; 20: 14118 – 14138

[2] Nour AMM et al. Planta Med 2009; 75: 1363 – 1368