Search for new antiprotozoal leads in oleo-gum-resins from plants of the family Burseraceae: Indian frankincense and myrrh

Malaria and the neglected tropical diseases sleeping sickness, Chagas disease and Leishmaniasis are infectious diseases that endanger millions of lives in the world, especially in poor regions. Because of the increase of resistances and high toxicity of existing medications there is an urgent need for new leads and agents against the pathogens causing these illnesses [1, 2]. In the course of our current search for natural products with this aim, Indian frankincense and myrrh, two oleo-gum-resins from plants of the family Burseraceae, showed antiprotozoal activity in vitro. While aqueous extracts where inactive, dichloromethane extracts showed the highest activity against Plasmodium falciparum (NF54 strain; IC₅₀= 2.58 µg/ml and 1.03 µg/ml, respectively) and to a lesser extent cytotoxicity against rat skeletal myoblasts (IC₅₀= 45.75 µg/ml and 8.50 µg/ml, resp.). Isolation of possible active compounds yielded some terpenoid substances, that where identified by spectroscopic measurements and comparison to data from literature. Cembrene A, 4,8,15,15-tetramethyl-12-methylene-bicyclo[9.3.1]pentadeca-3,7-diene, methyleugenol and 11-keto-β-boswellic acid were obtained from Indian frankincense, elemyl acetate, mansumbinone, (5E,9E)-8,11-dihydro-3,6,10-trimethyl-cyclodeca[b]furan-4(7 H)-one, (5Z,9Z)-8,11-dihydro-3,6,10-trimethyl-cyclodeca[b]furan-4(7 H)-one and 4,7,8,11-tetrahydro-8-methoxy-3,6,10-trimethyl-cyclodeca[b]furan from myrrh. All substances were tested for antiprotozoal activity in vitro using established protocols [3]. The best effect against Plasmodium falciparum so far was achieved by Cembrene A with an IC₅₀ value of 2.78 µg/ml. Bioactivity-guided fractionation of further active fractions is in progress.

Acknowledgements: This project is an activity within the Research Network Natural Products against Neglected Diseases (ResNet NPND; http://www.resnetnpnd.org/). Financial support by Cusanuswerk is gratefully acknowledged.

Keywords: Bioactivity-guided fractionation, antiprotozoal activity, myrrh, frankincense, Burseraceae, neglected tropical diseases.

References:

[1] Schmidt TJ, Khalid SA, Romanha AJ, Alves TMA, Biavatti MW, Brun R, da Costa FB, de Castro SL, Ferreira VF, de Lacerda MVG et al. The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases – Part I. Curr Med Chem 2012; 19: 2128 – 2175

[2] Schmidt TJ, Khalid SA, Romanha AJ, Alves TMA, Biavatti MW, Brun R, da Costa FB, de Castro SL, Ferreira VF, de Lacerda MVG et al. The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases – Part II. Curr Med Chem 2012; 19: 2176 – 2228

[3] Schmidt TJ, Nour AMM, Khalid SA, Kaiser M, Brun R. Quantitative Structure-Antiprotozoal Activity Relationships of Sesquiterpene Lactones. Molecules 2009; 14: 2062 – 2076