The differentiation-inducing factor-1 (DIF-1) is a lipophilic signal molecule (chlorinated alkylphenone) that induces stalk cell differentiation in the cellular slime mold Dictyostelium discoideum. in addition, DIF-1 and its derivatives have been shown to possess anti-leukemic activity and glucose Consumption-promoting activity in vitro in mammalian cells. In this study. to assess the chemical structure-effect relationship of DIF-1, we synthesized eight derivatives of DIF-1 and investigated their stalk cell-inducing activity in Dictyostelium cells and pharmacological activities in mammalian cells. Of the derivatives, two amide derivatives of DIF-1, whose hydrophobic indexes are close to that of DIF-1. induced stalk cell differentiation as strongly as DIF-1 in Dictyostelium cells. It Was also found that some derivatives Suppressed cell growth in human K562 leukemia cells and promoted glucose consumption in mouse 3T3-L1 cells. These results give LIS valuable information as to the chemical structure-effect relationship of DIF-1. (C) 2008 Elsevier Inc. All rights reserved.