Wei Linyi, Brossi Arnold, Kendall Ross, Bastow Kenneth F, Morris-Natschke Susan L, Shi Qian, Lee Kuo-Hsiung
Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
Bioorg Med Chem. 2006 Oct 1;14(19):6560-9. doi: 10.1016/j.bmc.2006.06.009. Epub 2006 Jun 30.
Polar phenanthrene-based tylophorine derivatives (PBTs) were designed, synthesized and evaluated as potential antitumor agents. These compounds contain a core phenanthrene structure and can be synthesized efficiently in excellent yield. The newly synthesized PBTs were evaluated for cytotoxic activity against the A549 human cancer cell line. Among them, N-(2,3-methylenedioxy-6-methoxy-phenanthr-9-ylmethyl)-L-2-piperidinemethanol (34) and N-(2,3-methylenedioxy-6-methoxy-phenanthr-9-ylmethyl)-5-aminopentanol (28) showed the highest potency with IC50 values of 0.16 and 0.27 microM, respectively, which are comparable to those of currently used antitumor drugs. A structure-activity relationship (SAR) study was also explored to facilitate the further development of this new compound class.
设计、合成并评估了基于菲的极性娃儿藤碱衍生物（PBTs）作为潜在的抗肿瘤药物。这些化合物含有一个核心菲结构，并且能够以优异的产率高效合成。对新合成的PBTs针对A549人癌细胞系的细胞毒性活性进行了评估。其中，N-(2,3-亚甲二氧基-6-甲氧基-菲-9-基甲基)-L-2-哌啶甲醇（34）和N-(2,3-亚甲二氧基-6-甲氧基-菲-9-基甲基)-5-氨基戊醇（28）表现出最高的效力，IC50值分别为0.16和0.27微摩尔，这与目前使用的抗肿瘤药物相当。还进行了构效关系（SAR）研究以促进这一新化合物类别的进一步开发。
