1. Academic Validation
  2. Synthesis and antitumor activity of the hexacyclic camptothecin derivatives

Synthesis and antitumor activity of the hexacyclic camptothecin derivatives

  • Bioorg Med Chem Lett. 2005 Jul 1;15(13):3233-6. doi: 10.1016/j.bmcl.2005.04.063.
Heyong Gao 1 Xiongwen Zhang Yi Chen Hongwu Shen Tao Pang Jing Sun Chenghui Xu Jian Ding Chuan Li Wei Lu
Affiliations

Affiliation

  • 1 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.

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