Department of Chemistry, Faculty of Science, Silpakorn University.
Chem Pharm Bull (Tokyo). 2022;70(7):483-491. doi: 10.1248/cpb.c22-00140.
The first total syntheses of natural phenanthrene alkaloids, namely, uvariopsamine (1), noruvariopsamine (2), 8-hydroxystephenanthrine (3), 8-methoxyuvariopsine (4), thalihazine (5), and secophoebine (6), have been realized. In addition, their in vitro antimalarial activity against the multidrug-resistant K1 strain of Plasmodium falciparum and in vitro cytotoxic activity against the human nasopharynx carcinoma (KB), small cell lung cancer (NCI-H187), and breast cancer (MCF7) human cancer cell lines were investigated. All the phenanthrene alkaloids showed significant antiplasmodial activity (IC 1.07-7.41 µM), and most compounds displayed low to no toxicity against the three cancer cell lines tested. Particularly, 3 exhibited the best antimalarial activity with an IC value of 1.07 µM, no toxicity to NCI-H187 (IC > 50 µM), and low toxicity against KB (IC 24.53 µM) and MCF7 (IC 42.67 µM) cell lines.
天然菲啶生物碱的首次全合成，即，乌头宁（1）、去乌头宁（2）、8-羟基石松宁（3）、8-甲氧基乌头宁（4）、紫堇嗪（5）和二氢血根碱（6），已经实现。此外，还研究了它们对耐多药恶性疟原虫 K1 株的体外抗疟活性和对人鼻咽癌细胞（KB）、小细胞肺癌（NCI-H187）和乳腺癌（MCF7）人癌细胞系的体外细胞毒性。所有菲啶生物碱均表现出显著的抗疟活性（IC 1.07-7.41 μM），并且大多数化合物对测试的三种癌细胞系显示出低毒性或无毒性。特别是，化合物 3 表现出最好的抗疟活性，IC 值为 1.07 μM，对 NCI-H187（IC > 50 μM）无毒性，对 KB（IC 24.53 μM）和 MCF7（IC 42.67 μM）细胞系的毒性较低。
