Bioactive flavaglines: Synthesis and pharmacology

Flavaglines represent a family of more than 100 cyclopenta[b]benzofurans that are found in medicinal plants of the genus Aglaia in South-East Asia. These compounds display potent anti-inflammatory, neuroprotective, cardioprotective, and above all, anticancer activities. The most amazing feature of flavaglines is their ability to kill cancer cells without affecting normal cells. Additionally, flavaglines protect neurons and cardiac cells from many types of stresses. Such a selective cytotoxicity to cancer cells and cytoprotection of normal cells, both of which occur at nanomolar concentrations, is unprecedented. This unique pharmacological profile of activity is now being rationalized with the recent discovery of their molecular targets, the scaffold proteins prohibitins and the translation initiation factor eIF4A (eukaryotic initiation factor-4A). This chapter aims to describe the synthetic routes to flavaglines, their mechanism of action, the evaluation of their biological potency, and ongoing effort to provide novel therapeutic agents.