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.
Richard L Alexander  1 ,  Susan L Morris-Natschke ,  Khalid S Ishaq ,  Ronald A Fleming ,  Gregory L Kucera
Affiliations
  • 1. Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27517, USA.
PMID: 12954073 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.