Quassinoids: From Traditional Drugs to New Cancer Therapeutics

G.      Fiaschetti; M.      A. Grotzer; T.      Shalaby; D.      Castelletti; A.      Arcaro

Abstract

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.

Keywords: Anticancer therapeutics, quassinoids, Simaroubaceae, tumor, Natural products, medicinal agents, antineoplastic proper-ties, anti-inflammatory activities, anti-viral, anti-ulcer, biogenesis, isolated, anti-cancer activity, peptidyl-transferase site, peptide bond formation, polarization, nucleic acid, carcinogenesis, oxygen-methylene bridge, C-ring, Ethiopia, bruceantin, breast cancer, hypotension, vomiting, lymphoma, myeloma cell lines, apoptosis in leukemia cells, death, oncogene, RNA transcripts, post-translational levels, malaria, ethanolic extract of Brucea, cell proliferation, human pancreatic adenocarcinoma, fibroblasts, condensation, glutathione, leukemic cell, Phosphorylation, translocation of NF-B, chemopreventive agents, brusatol, glycosylation, epoxy-methano bridge, ester, lipophilicity, alkyl groups, hydroxyl substituents, ester side chain, potency, eurycomalide, Eurycoma longifolia, breast carcinoma, proteins, Ailanthus altissima, Simaroubaceae family, tigloyloxychaparrinone, hypoxia, endothelial growth factor, tigloyloxy group, leukemic cells, lipophilic ester side chain, extracellular signal-regulated kinase