Synthesis and antitumor activity of the hexacyclic camptothecin derivatives |
| |
Authors: | Gao Heyong Zhang Xiongwen Chen Yi Shen Hongwu Pang Tao Sun Jing Xu Chenghui Ding Jian Li Chuan Lu Wei |
| |
Affiliation: | Shanghai Institute of Materia Medica, SIBS, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 555, Zuchongzhi Road, Zhangjiang High-Tech Park, Shanghai 201203, China. |
| |
Abstract: | A series of hexacyclic camptothecin derivatives were synthesized to test for antitumor activity as topoisomerase I inhibitor. The strategy of synthesis was used for the formation of additional furan and dihydrofuran rings fused with 9- and 10-positions of camptothecin. All of the hexacyclic camptothecins were assayed for cytotoxicity against four human tumor cell lines, HL60, BEL-7402, HCT-116, and HeLa, and showed very impressive cytotoxicity activity in vitro. Enzyme activity of the hexacyclic camptothecins was evaluated, being equal or superior to that of SN-38. The stability of four compounds was assessed in human plasma. Two of these compounds were chosen to test for antitumor activity in vivo against Sarcoma-180. The results suggested that additional furan and dihydrofuran rings could improve the antitumor activity in vitro and vivo, though the stability of the lactone ring did not increase. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|