Design, synthesis and identification of novel colchicine-derived immunosuppressant.
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.
Chang
Dong-Jo
DJ
College of Pharmacy, Seoul National University, San 56-1, Sillim-dong, Gwanak-gu, Seoul 151-742, Republic of Korea.
Yoon
Eun-Young
EY
Lee
Geon-Bong
GB
Kim
Soon-Ok
SO
Kim
Wan-Joo
WJ
Kim
Young-Myeong
YM
Jung
Jong-Wha
JW
An
Hongchan
H
Suh
Young-Ger
YG
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003078:Colchicine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D015195:Drug Design; D006074:Gout Suppressants / Q000138:chemical synthesis / Q000494:pharmacology; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D007249:Inflammation; D020128:Inhibitory Concentration 50; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D051381:Rats; D016038:Skin Transplantation; D013329:Structure-Activity Relationship
D006074:Gout Suppressants; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003078:Colchicine