Synthesis and antitumor activity of 7-ethyl-9-alkyl derivatives of camptothecin

Bioorg Med Chem Lett. 2005 Apr 15;15(8):2003-6. doi: 10.1016/j.bmcl.2005.02.072.

Abstract

A series of new camptothecin derivatives, as topoisomerase I inhibitor, were synthesized to identify potent antitumor agents. The synthesis method was based on the Claisen rearrangement of 10-allyloxy-7-ethylcamptothecin. All of the compounds were assayed for cytotoxicity against two human tumor cell lines, Bel7402, HCT116, and showed good potency in vitro. Compounds 2, 4, 9, were assessed for the stability of lactone in human plasma. And then compound 2 was tested for antitumor activity in vitro against mouse tumor sarcoma-180. The results suggested that the small alkyl groups in the both 7- and 9-positions of camptothecin could promote liposolubility, antitumor activity in vitro and vivo, though did not bring much increase of the stability of lactone.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemical synthesis*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Camptothecin / analogs & derivatives*
  • Camptothecin / chemical synthesis*
  • Camptothecin / pharmacology
  • Cell Line, Tumor
  • Humans

Substances

  • Antineoplastic Agents, Phytogenic
  • Camptothecin