title: Anti-tumor agents 255: novel glycyrrhetinic acid-dehydrozingerone conjugates as cytotoxic agents.
abstract: Esterification of glycyrrhetinic acid (GA) with dehydrozingerone (DZ) resulted in a novel cytotoxic GA-DZ conjugate. Based on this exciting finding, we conjugated eleven different DZ analogs with GA or other triterpenoids, including oleanoic acid (OA) or ursolic acid (UA). In an in vitro anti-cancer assay using nine different human tumor cell lines, most of the GA-DZ conjugates showed significant potency. Particularly, compounds 5, 29, and 30 showed significant cytotoxic effects against LN-Cap, 1A9, and KB cells with ED(50) values of 0.6, 0.8, and 0.9 microM, respectively. Similar conjugates between DZ and OA or UA were inactive suggesting that the GA component is critical for activity. Notably, although GA-DZ conjugates showed potent cytotoxic activity, the individual components (GA and DZ analogs) were inactive. Thus, GA-DZ conjugates are new chemical entities and represent interesting hits for anti-cancer drug discovery and development.
authors.affiliation: Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7360, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Tatsuzaki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Bastow
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakagawa-Goto
authors.forename: Susan L
authors.initials: SL
authors.lastname: Morris-Natschke
authors.forename: Hideji
authors.initials: H
authors.lastname: Itokawa
authors.forename: Kimiye
authors.initials: K
authors.lastname: Baba
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006034:Glycyrrhetinic Acid / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship; D013343:Styrenes / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D013343:Styrenes; C052933:methyl-3-methoxy-4-hydroxystyryl ketone; D006034:Glycyrrhetinic Acid