Evaluation of antiplasmodial activity of five sudanese medicinal plants on the basis of enoyl-ACP reductase (PfENR) inhibition

Plasmodium falciparum is the most serious health threat in Sub-Saharan Africa¹. This situation is further aggravated by the resistance to currently known antimalarials coupled with the lack of an effective vaccine. Therefore, there is an urgent need to discover new viable biochemical targets and biologically active compounds. The discovery of a type II fatty acid biosynthesis pathway (FAS II) in P. falciparum, particularly, the enoyl-ACP reductase (PfENR), which catalyses the rate limiting step in each elongation circle, has been recognized and validated as an important target^2,3. The present work capitalizes on the discovery of new antimalarial molecules based on PfENR inhibition.

The alcoholic extracts of five plants commonly used in the Sudanese traditional medicine to treat malaria exhibited certain degree of inhibition of PfENR in concentration less than 250 µg/mL. Bioactivity-guided fractionation revealed that the most potent inhibitors of PfENR were the ethyl acetate fraction of Acacia nilotica and Khaya senegalensis stem barks followed by their water residue and finally the Ziziphus spina-christi root bark with an IC₅₀ of 0.87, 3.35, 6.33, 11.68 and 15.62 µg/mL respectively. The very prominent activity of the ethyl acetate fraction of Acacia nilotica had encouraged us to further analyze it in order to isolate bioactive compound(s) associated with the aforementioned activity.

References:

[1] World malaria report: 2012. WHO

[2] Freundlich, J. S.; Anderson, J. W.; Sarantakis, D.; Shieh, H.-M.; Yu, M.; Valderramos, J.-C.; Lucumi, et al., Bioorg. Med. Chem. Lett. 2005, 15, 5247 – 52.

[3] Perozzo, R.; Kuo, M.; Sidhu, A. B. S.; Valiyaveettil, J. T.; Bittman, R.; Jacobs, W. R.; et al., Biol. Chem. 2002, 277, 13106 – 14.