Synthesis and cytotoxicity of new aromatic ceramide analogs with alkylsulfonamido chains.

A series of D-erythro ceramide analogues, N-(2S, 3R, 4E)-1, 3-dihydroxy-5-phenyl pent-4-en-2-yl alkyl sulfonamides, were synthesized and evaluated for their in vitro cytotoxic activities against five human tumor cell lines. The aromatic sulfon amido ceramide analogue (10f) showed more potent cytotoxic activity than that of the B13, indicating that a sulfonamide group appears to serve as a bioisostere of an amide in drug design. Variations in the alkyl sulfonyl chain length significantly influenced the cytotoxic activity of the sulfonamido ceramide analogues, but the introduction of a para halogen on the phenyl ring of aromatic ceramide analogues had no affect on the activity.