Muhammad Ilias, Dunbar D Chuck, Khan Shabana I, Tekwani Babu L, Bedir Erdal, Takamatsu Satoshi, Ferreira Daneel, Walker Larry A
National Center for Natural Products Research and Department of Pharmacology, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, Mississippi 38677, USA.
J Nat Prod. 2003 Jul;66(7):962-7. doi: 10.1021/np030086k.
Psychotria klugii yielded two new benzoquinolizidine alkaloids, klugine (1) and 7'-O-demethylisocephaeline (2), together with the previously known cephaeline (3), isocephaeline (4), and 7-O-methylipecoside (5). The structures and stereochemistry of 1 and 2 were determined by 1D and 2D NMR data and circular dichroism experiments. Cephaeline (3) demonstrated potent in vitro antileishmanial activity against Leishmania donavani (IC(50) 0.03 microg/mL) and was >20- and >5-fold more potent than pentamidine and amphotericin B, respectively, while klugine (1) (IC(50) 0.40 microg/mL) and isocephaeline (4) (IC(50) 0.45 microg/mL) were <13- and <15-fold less potent than 3. In addition, emetine (6) (IC(50) 0.03 microg/mL) was found to be as equally potent as 3, but was >12-fold more toxic than 3 against VERO cells (IC(50) 0.42 vs 5.3 microg/mL). Alkaloids 1 and 3 exhibited potent antimalarial activity against Plasmodium falciparum clones W2 and D6 (IC(50) 27.7-46.3 ng/mL). Compound 3 was cytotoxic to SK-MEL, KB, BT-549, and SK-OV-3 human cancer cells, while 1 was inactive.
克鲁吉九节木（Psychotria klugii）产生了两种新的苯并喹嗪啶生物碱，克鲁吉宁（1）和7'-O-去甲基异吐根酚碱（2），以及先前已知的吐根酚碱（3）、异吐根酚碱（4）和7-O-甲基脂麻苷（5）。通过一维和二维核磁共振数据以及圆二色性实验确定了1和2的结构及立体化学。吐根酚碱（3）对杜氏利什曼原虫显示出强大的体外抗利什曼活性（IC50为0.03μg/mL），分别比喷他脒和两性霉素B强20倍以上和5倍以上，而克鲁吉宁（1）（IC50为0.40μg/mL）和异吐根酚碱（4）（IC50为0.45μg/mL）的活性分别比3低13倍和15倍以下。此外，依米丁（6）（IC50为0.03μg/mL）的活性与3相当，但对VERO细胞的毒性比3高12倍以上（IC50分别为0.42μg/mL和5.3μg/mL）。生物碱1和3对恶性疟原虫克隆W2和D6表现出强大的抗疟活性（IC50为27.7 - 46.3 ng/mL）。化合物3对SK-MEL、KB、BT-549和SK-OV-3人癌细胞具有细胞毒性，而1无活性。
