Cytostatic activity of new synthetic anti‐tumor aza‐alkyllysophospholipids

Alkyllysophospholipids are analogues of the naturally occurring 2‐lysophosphatidylcholine which have been reported to have selective in vitro/in vivo anti‐tumor activity. Their anti‐proliferative effect has been found against a variety of animal and human tumor cell lines. We have characterized the cytostatic activity of 2 newly synthetized aza‐alkyllysophospholipids (AALPs), the BN52205 and the BN52211, on a human tumor cell line derived from a colon adenocarcinoma, the HT29. We used 3 different flow cytometric approaches to study which phase of the cell cycle was the most sensitive to the anti‐proliferative activity of the 2 AALPs. By applying the biparametric analysis of 5′‐bromo‐2‐deoxyuridine incorporation vs . DNA content we have been able to demonstrate that the 2 AALPs do not interfere with the S phase of the cell cycle. The simultaneous measurement of total nuclear protein vs . DNA content in isolated HT29 nuclei enabled us to exclude a block in the M phase of the ee cycle. Finally, stathmokinetic analysis enabled us to show that cytostatic activity of the 2 new AALPs is characterized by multiple “terminal points” as the drugs' action results in a G 1 block, in a slow‐down of the transition from late S to G 2 followed by an accumulation of HT29 cells in the G 2 phase of the cell cycle. © 1992 Wifey‐Liss, Inc.