Phosphate ester derivatives of homocamptothecin: synthesis, solution stabilities and antitumor activities

Bioorg Med Chem. 2010 May 1;18(9):3140-6. doi: 10.1016/j.bmc.2010.03.039. Epub 2010 Mar 20.

Abstract

Homocamptothecins (hCPTs) represents a new promising class of topoisomerase I inhibitors with enhanced stability and superior antitumor activity. Some phosphodiesters and phosphotriesters homocamptothecin derivatives were designed and synthesized based on our previous synthetic route. The cytotoxicity in vitro on three cancer cell lines and antitumor activity in vivo, and inhibitory properties of topoisomerase I of these derivatives were evaluated. Among them compounds 24e and 24f exhibited higher cytotoxic activity than IRT and the former exhibited the best antitumor activity in vivo and solution stability both at pH 7.4 and pH 3.0.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Camptothecin / analogs & derivatives*
  • Camptothecin / chemical synthesis
  • Camptothecin / chemistry
  • Camptothecin / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Drug Stability
  • Esters* / chemical synthesis
  • Esters* / chemistry
  • Esters* / pharmacology
  • Humans
  • Hydrogen-Ion Concentration
  • Inhibitory Concentration 50
  • Molecular Structure
  • Pharmaceutical Solutions
  • Phosphates* / chemical synthesis
  • Phosphates* / chemistry
  • Phosphates* / pharmacology
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Esters
  • Pharmaceutical Solutions
  • Phosphates
  • homocamptothecin
  • Camptothecin