Quassinoids are a group of compounds extracted from plants of the Simaroubaceae family, which have been used for many years in
folk medicine. These molecules gained notoriety after the initial discovery of the anti-leukemic activity of one member,
bruceantin, in 1975. Currently over 150
quassinoids have been isolated and classified based on their chemical structures and
biological properties investigated in vitro and in vivo. Many molecules display a wide range of inhibitory effects, including anti-inflammatory, anti-viral,
anti-malarial and anti-proliferative effects on various
tumor cell types. Although often the exact mechanism of action of the single agents remains unclear, some agents have been shown to affect
protein synthesis in general, or specifically HIF-1α and MYC, membrane polarization and the apoptotic machinery. Considering that future research into chemical modifications is likely to generate more active and less toxic derivatives of natural
quassinoids, this family represents a powerful source of promising small molecules targeting key prosurvival signaling pathways relevant for diverse pathologies. Here, we review available knowledge of functionality and possible applications of
quassinoids and
quassinoid derivatives, spanning traditional use to the potential impact on modern medicine as
cancer therapeutics.