176776-97-9Relevant academic research and scientific papers
Synthesis of liposomal phospholipid-(N4-palmitoyl-1-β-D-arabinofuranosylcytosine) conjugates and evaluation of their cytostatic activity against L1210 murine leukemia
Schott, Herbert,Schwendener, Reto A.
, p. 365 - 369 (2007/10/03)
N4-Palmitoyl-araC, a prodrug of the cytostatic compound 1-β-D-arabinofuranosylcytosine (araC), was linked by means of the triester method to the phospholipids (2-chlorophenyl) (1,2-di-O-palmitoylglyceryl) phosphate, (2-chlorophenyl) (1,2-di-O-octadecylglyceryl) phosphate and (2-chlorophenyl) (1-O-octadecyl-2-O-palmitoylglyceryl) phosphate. In the first step of these gram-scale syntheses phospholipid-(N4-palmitoyl-araC) conjugates were obtained the linkage of which was accomplished via a triester group. In the second step the final condensates were obtained through transformation of the triester into a diester linkage by removal of the 2-chlorophenyl group. The cytostatic activity of these compounds which form stable liposomal preparations together with matrix lipids was evaluated according to the L1210 mouse leukemia model. The conjugates containing a triester linkage were shown to be ineffective, whereas those with a diester linkage display a significantly higher antitumor activity as compared to N4-palmitoyl-araC and araC. With the diester 6a-8a 80-100% of the treated animals were cured at a total dose of 200 μmol/kg, whereas with araC given at a fourfould higher concentration none of the treated mice survived. VCH Verlagsgesellschaft mbH, 1996.
