Evaluation of the Anti-Plasmodial Activity of Bisbenzylisoquinoline Alkaloids from Abuta grandifolia

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Abstract
Three alkaloids were isolated from the bark of the traditional medicinal plant Abuta grandifolia (Mart.) Sandw. (Menispermaceae) and tested for in vitro anti-plasmodial activity. Two of them were identified as the Type VIII bisbenzylisoquinoline alkaloids, krukovine (1) and limacine (2), while the least abundant compound (3) could only be characterised to Type I of the same class. Krukovine exhibited potent anti-plasmodial activity with IC50 values of 0.44 μg/ml and 0.022 μg/ml against K1 (chloroquine-resistant) and T9-96 (chloroquine-sensitive) Plasmodium falciparum, respectively. Both limacine and compound 3 exhibited moderate anti-plasmodial activity against K1 with IC 50 values of 1.35 μg/ml and 1.58 μg/ml, respectively. Limacine gave an IC50 value of 0.24 μg/ml against T9-96. Krukovine and limacine showed greater activity against T9-96 than against K1, exhibiting similar activity profiles to that of chloroquine diphosphate (0.187 μg/ml and 0.013 μg/ml against K1 and T9-96, respectively). This indicates that krukovine and limacine may be affected by the mechanism of chloroquine resistance present in K1 P. falciparum .

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