Synthesis and Biological Evaluation of Dimeric Furanoid Macroheterocycles: Discovery of New Anticancer Agents

A recently developed dimerization/macrocyclization
was employed
to synthesize a series of macroheterocycles which were biologically
evaluated, leading to the discovery of a number of potent cytotoxic
agents (e.g., 27: GI50 = 51 nM against leukemia
CCRF-CEM cell line; 29: GI50 = 99 nM against
melanoma MDA-MB-435 cell line). Further biological studies support
an apoptosis mechanism of action for these compounds involving deregulation
of the tricarboxylic acid cycle activity and suppression of mitochondrial
function in cancer cells.