Synthesis and cytotoxic activity of two novel 1-dodecylthio-2-decyloxypropyl-3-phosphatidic acid conjugates with gemcitabine and cytosine arabinoside

J Med Chem. 2003 Sep 11;46(19):4205-8. doi: 10.1021/jm020571x.

Abstract

Cytosine arabinoside (ara-C) and gemcitabine (dFdC) are two standard chemotherapy drugs used in the treatment of patients with various cancers. To alter the pharmacokinetic and pharmacodynamic properties of these molecules, we conjugated a synthetic phospholipid to both ara-C and dFdC and investigated their chemotherapeutic potential. The dFdC conjugate had greater cytotoxic activity compared with the ara-C conjugate and demonstrated notable cytotoxicity against all human cell lines tested.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Buffers
  • Cell Line
  • Cytarabine / analogs & derivatives*
  • Cytarabine / pharmacology
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / chemistry*
  • Deoxycytidine / pharmacology
  • Gemcitabine
  • Humans
  • Inhibitory Concentration 50
  • Phosphatidic Acids / chemical synthesis
  • Phosphatidic Acids / chemistry*
  • Phosphatidic Acids / pharmacokinetics
  • Phosphatidic Acids / pharmacology*
  • Ribonucleotide Reductases / antagonists & inhibitors
  • Solubility

Substances

  • Antineoplastic Agents
  • Buffers
  • Phosphatidic Acids
  • Cytarabine
  • Deoxycytidine
  • Ribonucleotide Reductases
  • Gemcitabine