Steele J C, Simmonds M S, Veitch N C, Warhurst D C
Jodrell Laboratory, Royal Botanic Gardens, Kew, Richmond, Surrey, U.K.
Planta Med. 1999 Jun;65(5):413-6. doi: 10.1055/s-1999-14017.
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.
从传统药用植物大叶阿木藤（Abuta grandifolia (Mart.) Sandw.）（防己科）的树皮中分离出三种生物碱，并对其体外抗疟活性进行了测试。其中两种被鉴定为VIII型双苄基异喹啉生物碱，即克鲁科文（1）和利马辛（2），而含量最少的化合物（3）仅能被鉴定为同一类别的I型。克鲁科文表现出较强的抗疟活性，对恶性疟原虫K1株（氯喹耐药）和T9-96株（氯喹敏感）的IC50值分别为0.44微克/毫升和0.022微克/毫升。利马辛和化合物3对K1株均表现出中等抗疟活性，IC50值分别为1.35微克/毫升和1.58微克/毫升。利马辛对T9-96株的IC50值为0.24微克/毫升。克鲁科文和利马辛对T9-96株的活性比对K1株的活性更强，其活性谱与磷酸二氢氯喹相似（对K1株和T9-96株的IC50值分别为0.187微克/毫升和0.013微克/毫升）。这表明克鲁科文和利马辛可能受到K1恶性疟原虫中存在的氯喹耐药机制的影响。
