Design, synthesis and identification of novel colchicine-derived immunosuppressant

A new class of immunosuppressant on the structural basis of colchicines is reported. In particular, analog 20a exhibited excellent immunosuppressant activity comparable to that of cyclosporin A. Synthesis and biological evaluation of various colchicine analogues through the mixed-lymphocyte reaction (MLR), lymphoproliferation, and inhibitory effects on the inflammatory genes are described. In addition, a new series of immunosuppressive agents developed on the structural basis of colchicine, as well as their structure–activity relationships is reported. The most potent analogue 20a exhibited an excellent immunosuppressive activity on in vivo skin-allograft model, which is comparable to that of cyclosporin A.