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Quassinoids: From Traditional Drugs to New Cancer Therapeutics

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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.

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

Document Type: Research Article

Publication date: 2011-01-01

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