Synthesis and cytotoxic activity of two novel 1-dodecylthio-2-decyloxypropyl-3-phosphatidic acid conjugates with gemcitabine and cytosine arabinoside.
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.
Alexander
Richard L
RL
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27517, USA.
Morris-Natschke
Susan L
SL
Ishaq
Khalid S
KS
Fleming
Ronald A
RA
Kucera
Gregory L
GL
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002021:Buffers; D002460:Cell Line; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D010712:Phosphatidic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D012995:Solubility; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D002021:Buffers; D010712:Phosphatidic Acids; D003561:Cytarabine; D003841:Deoxycytidine; D012264:Ribonucleotide Reductases; D000093542:Gemcitabine