Improved synthesis of 6-epi-dictyostatin and antitumor efficacy in mice bearing MDA-MB231 human breast cancer xenografts.
Structure-activity studies centered on the naturally occurring antitumor agent dictyostatin have recently identified several highly active epimers and analogues. From these compounds, 6- epi-dictyostatin was selected for scaleup preparation and evaluation in animals. Here we describe a new total synthesis that produced more than 30 mg of 6- epi-dictyostatin. The compound was found to have potent antitumor activity in SCID mice bearing MDA-MB231 human breast cancer xenografts.
Department of Pharmacology & Chemical Biology and University of Pittsburgh Cancer Institute, G.27.b Research Pavilion, Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, Pennsylvania 15213-1862, USA. eisemanj@msx.upmc.edu
Julie L
JL
Eiseman
Lihua
L
Bai
Won-Hyuk
WH
Jung
Gustavo
G
Moura-Letts
Billy W
BW
Day
Dennis P
DP
Curran
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D051379:Mice; D023041:Xenograft Model Antitumor Assays
D018942:Macrolides; C470814:dictyostatin