Digalloyl Glycoside: A Potential Inhibitor of Trypanosomal PFK from Euphorbia abyssinica J.F. Gmel.

Human African trypanosomiasis is an endemic infectious disease caused by Trypanosoma brucei via the bite of tsetse-fly. Most of the drugs used for the treatment, e.g., Suramin, have shown several problems, including the high level of toxicity. Accordingly, the discovery of anti-trypanosomal drugs from natural sources has become an urgent requirement. In our previous study on the anti-trypanosomal potential of Euphorbia species, Euphorbia abyssinica displayed significant anti-trypanosomal activity. Therefore, a phytochemical investigation of the methanolic extract of E. abyssinica was carried out. Twelve compounds, including two triterpenes ( 1 , 2 ); one sterol-glucoside ( 4 ); three ellagic acid derivatives ( 3 , 9 , 11 ); three gallic acid derivatives ( 5 , 6 , 10 ); and three flavonoids ( 7 , 8 , 12 ), were isolated. The structures of isolated compounds were determined through different spectroscopic techniques. Compound ( 10 ) was obtained for the first time from genus Euphorbia while all other compounds except compound ( 4 ), were firstly reported in E. abyssinica . Consequently, an in silico study was used to estimate the anti-trypanosomal activity of the isolated compounds. Several compounds displayed interesting activity where 1,6-di- O -galloyl-d-glucose ( 10 ) appeared as the most potent inhibitor of trypanosomal phosphofructokinase (PFK). Moreover, molecular dynamics (MD) simulations and ADMET calculations were performed for 1,6-di- O -galloyl-d-glucose. In conclusion, 1,6-di- O -galloyl-d-glucose revealed high binding free energy as well as desirable molecular dynamics and pharmacokinetic properties; therefore, it could be suggested for further in vitro and in vivo studies for trypanosomiasis.