STRUCTURE-FUNCTION-RELATIONSHIPS OF ALKYL-LYSOPHOSPHOLIPID ANALOGS INSELECTIVE ANTITUMOR-ACTIVITY

This investigation was initiated in order to delineate the structure-f unction relationship of the anticancer alkyl-lysophospholipids and ass ess their degree of selective cytotoxicity toward neoplastic cells. A series of glycerol phosphocholine analogs with varying substitutions i n the sn-1 and sn-2 position were tested for their inhibitory activity as measured by thymidine incorporation, clonogenic assays and effects on protein kinase C activity against a series of human leukemic cell lines and healthy bone marrow progenitor cells. The IC50 was determine d for each of the compounds in each cell line and healthy bone marrow cells following a 4-h incubation. The data indicated that a 16-18 carb on chain at the sn-1 coupled with a short substitution at sn-2 had the broadest antitumor activity and was the least toxic to normal bone ma rrow cells. The results provide a number of useful leads toward the de sign and development of potentially more active phospholipid compounds .