Evaluation of the anti-plasmodial activity of bisbenzylisoquinoline alkaloids from Abuta grandifolia.
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 microgram/ml and 0.022 microgram/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 IC50 values of 1.35 micrograms/ml and 1.58 micrograms/ml, respectively. Limacine gave an IC50 value of 0.24 microgram/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 microgram/ml and 0.013 microgram/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.
Steele
J C
JC
Jodrell Laboratory, Royal Botanic Gardens, Kew, Richmond, Surrey, U.K.
Simmonds
M S
MS
Veitch
N C
NC
Warhurst
D C
DC
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D000818:Animals; D000962:Antimalarials / Q000633:toxicity*; D002738:Chloroquine / Q000633:toxicity; D007546:Isoquinolines / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D015394:Molecular Structure; D010936:Plant Extracts; D010946:Plants, Medicinal; D010963:Plasmodium falciparum / Q000187:drug effects*; D014197:Trees
D000470:Alkaloids; D000962:Antimalarials; D007546:Isoquinolines; D010936:Plant Extracts; D002738:Chloroquine