School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China.
Eur J Med Chem. 2010 Apr;45(4):1515-23. doi: 10.1016/j.ejmech.2009.12.060. Epub 2010 Jan 13.
The beta-carboline alkaloids have been characterized as a class of potential antitumor agents. To further enhance the cytotoxic potency and improve water solubility of beta-carboline, a series of new beta-carboline amino acid ester, beta-carboline amino acid and N(2)-benzylated quaternary beta-carboline amino acid ester conjugates were designed and synthesized, and the cytotoxic activities of these compounds were evaluated using a panel of human tumor cell lines. The N(2)-benzylated quaternary beta-carboline amino acid ester conjugates represented the most interesting cytotoxic activities. Particularly, compounds 8b and 8g were found to be the most potent compounds with IC(50) values lower than 20 microM against all human tumor cell lines investigated. These results confirmed that the N(2)-benzyl substituent on the beta-carboline ring played an important role in the modulation of the cytotoxic potencies.
β-咔啉生物碱已被鉴定为一类具有潜在抗肿瘤活性的物质。为了进一步提高β-咔啉的细胞毒性和改善其水溶性，设计并合成了一系列新型的β-咔啉氨基酸酯、β-咔啉氨基酸和 N(2)-苄基季铵化β-咔啉氨基酸酯缀合物，并通过一系列人肿瘤细胞系评估了这些化合物的细胞毒性。N(2)-苄基季铵化β-咔啉氨基酸酯缀合物表现出最有趣的细胞毒性活性。特别是，化合物 8b 和 8g 被发现是最有效的化合物，对所有研究的人肿瘤细胞系的 IC(50)值均低于 20μM。这些结果证实了β-咔啉环上的 N(2)-苄基取代基在调节细胞毒性方面发挥了重要作用。
