Antiplasmodial activity of constituents isolated from Croton lobatus

Seven constituents were isolated from the stems and leaves of Croton lobatus L. (Euphorbiaceae), a medicinal plant used in western Africa in traditional folk medicine to cure malaria, pregnancy troubles, and dysentery. Their structures were elucidated by spectroscopic methods. The compounds identified were3-[(6Z,9Z))dodeca-6,9-dienoyloxy]-2-octanoyloxypropyl(6Z,9Z)dodeca-6,9-dienoate (1) for the first time and six known compounds: (Z,Z,Z)-9,12,15-octadecatrienoic acid methyl ester (2), 8,11,17,2 1 -tetrame(-thyl-(E,E,E,E)-8,10,17,21-tetraentetracosanoic acid (3), geranylgeraniol (4), cholestan-3-one (5), betulinic acid (6), and (E)-3-(4-methoxy-phenyl)2-phenyl-acrylic acid (7). From the seven compounds, (4) and (6) showed the best antiplasmodial activity in vitro on Plasmodium falciparum KI chloroquine-resistant strain, with IC50 values (mu g/mL) of 1.07 and 1.45 mg/mL, respectively, while compounds (2), (3), and (7) showed IC50 below 5 in the same assay. Cytotoxicity of the most active compounds was evaluated on L6 murine myoblast cells. Geranylgeramol (4) showed good selectivity with an SI value (SI = ratio of cytotoxicity to biological activity) over 25.