The
sphingolipid metabolites have emerged as a starting point for the development of novel
therapeutics for many diseases. However, details of the functions and mechanisms of
sphingolipids remain unknown. To better understand the roles of
sphingolipids, chemical tools with unique
biological and physicochemical properties are needed. In this regard, we previously reported the synthesis of sphingoid base analogues in which the
carbon chains are restricted by triple bonds. Here, we have conjugated a
fluorescent dye to the
polyyne analogues of the sphingoid bases to generate optical probes. Like the parent
polyyne-containing sphingoid base, the
7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD)-labeled triyne-
sphingosine inhibited
cancer cell growth far more effectively than did the corresponding
sphingosine. NBD-triyne-
sphingosine was rapidly incorporated into the cells and displayed broad cytoplasmic distribution. According to the results of a flow cytometric analysis,
cancer cells fed with NBD-triyne-
sphingosine showed significantly increased fluorescence intensity compared with the NBD-
sphingosine treated cells. The metabolism of NBD-triyne-
sphingosine was somewhat different from that of NBD-
sphingosine. These results indicated that the incorporated rigid
polyyne moiety in the sphingoid base altered the physicochemical properties of the
sphingolipid, thereby affecting its
biological behavior. The higher antiproliferative activity in the SRB assay and the significantly higher fluorescence intensity observed in the flow cytometric analysis are some of the interesting and distinct aspects of NBD-triyne-
sphingosine compared to standard NBD-
sphingosine probes. Thus, it is believed that the fluorescently labeled
polyyne-containing sphingoid base developed in this study will be a useful chemical tool in
sphingolipid research.