Recent Advances in the Development of Polyamine Analogues as Antitumor Agents

摘要: Since the publication of our previous Perspective dealing with polyamine drug discovery,1 field has undergone numerous changes. Most prominent among these changes, from a medicinal chemistry point view, is that discovery efforts have partially shifted away an emphasis on inhibitors biosynthetic and catabolic enzymes. This shift in part due to fact multiple compensatory mechanisms are available able maintain homeostasis cellular pools,2 thus utility specific enzyme as drugs limited. Specific for every pathway,1, 3-6 transport system.7-9 Although significant effects their respective target enzymes, only one inhibitor, α-difluoromethylornithine (DFMO) reached market. DFMO was originally designed antitumor agent, but not effective enough warrant continued Phase II trials. However, it been shown be cure infection caused by Trypanosoma brucei gambiense (West African Sleeping Sickness),10, 11 recently considerable potential cancer chemopreventive agent (see below).12-14 no other biosynthesis inhibitor advanced market, ubiquitous nature natural polyamines would lead conclude molecules effector sites frequently dysregulated cancer, such should provide rich environment therapeutic intervention. Recent focused compounds produce either independent of, or addition metabolic In addition, chains used make hybrid order improve import, increase affinity chromatin serve carriers. will focus developments since article.1