Biological Activity of a New Ketone-Containing Analog of Edelfosine

We describe the preliminary biological studies with LM-1025, a new analog of ET-I8-OCH 3 (edelfosine) in which a ketone function has been introduced in the sn-1 alkyl chain. We have comparatively tested both compounds in a series of experiments directed to assess their cytotoxicity, their membranolytic activity, and their PAF-related effects. Our results indicate a very similar cytotoxic behavior for both compounds in the dose- and time-dependent tests, as well as in the selectivity assay using HL-60 cells, PMA-differentiated HL-60 cells, and a non-malignant cell line, RPMI-1788. LM-1025 differs from ET-I8-OCH 3 in showing a lower membranolytic effect on rat erythrocytes and in lacking of any PAF-agonistic effect.