Discovery of potent cell migration inhibitors through total synthesis: lessons from structure-activity studies of (+)-migrastatin.
Synthesis of highly active migrastatin-based tumor migration cell inhibitors has been accomplished. Our flexible and concise total synthesis of migrastatin has allowed us to explore otherwise inaccessible migrastatin-derived structural motifs. This effort has resulted in the discovery of analogues with tumor cell migration inhibitory activity 3 orders of magnitude higher than that of the natural product.
Njardarson
Jón T
JT
Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021, USA.
Gaul
Christoph
C
Shan
Dandan
D
Huang
Xin-Yun
XY
Danishefsky
Samuel J
SJ
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D015195:Drug Design; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D018942:Macrolides; D051379:Mice; D010881:Piperidones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D020533:Angiogenesis Inhibitors; D007783:Lactones; D018942:Macrolides; D010881:Piperidones; C418199:migrastatin