In vivo Antimalarial Evaluation of Embelin and its Semi-Synthetic Aromatic Amine Derivatives

Background: In less developed countries like Ethiopia, malaria is traditionally treated by remedies prepared from medicinal plants. One such plant that falls in this category is Embelia schimperi Vatke whose fruits are employed for the treatment of a variety of ailments including taeniasis and malaria. Objective: In the present study, the in vivo antimalarial activity of embelin isolated from the fruits of Embelia schimperi Vatke and its semisynthetic aromatic amine derivatives was evaluated. Methods: Silica gel column chromatography was used to isolate embelin from the ethyl acetate extract of the fruits of E. schimperi. Aromatic substituted embelin derivatives were semi-synthesized by using a one-step condensation reaction of embelin with aromatic amines. The compounds were characterized based on their UV, IR, HR-ESIMS, ¹H and ¹³C NMR and DEPT-135 spectral data. Antimalarial activity was evaluated using a modified Peter’s 4-day suppressive test against chloroquine sensitive Plasmodium berghei infection in mice. Results: Embelin and the semi-synthetic derivatives showed significant (p<0.05) in vivo antimalarial activity in a dose-dependent manner with 47.8-74.7% parasite suppression at tested doses of 100-400 mg/kg. Among the compounds semi-synthesized, 5-(p-tolylamino)-2-hydroxy-3-undecylcyclohexa- 2,5-diene-1,4-dione showed maximum antimalarial activity (74.7 % suppression) at a dose of 400 mg/kg. No major signs of toxicity were observed when either embelin or the semi-synthesized derivatives were administrated to mice at the highest tested dose (2 g/kg). Conclusion: The results underline that the antimalarial activity of embelin can be improved by preparing its aromatic semi-synthetic amine derivatives without affecting the safety of the parent molecule.