Anti-tumor agents 255: novel glycyrrhetinic acid-dehydrozingerone conjugates as cytotoxic agents.
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.
Tatsuzaki
Jin
J
Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7360, USA.
Taniguchi
Masahiko
M
Bastow
Kenneth F
KF
Nakagawa-Goto
Kyoko
K
Morris-Natschke
Susan L
SL
Itokawa
Hideji
H
Baba
Kimiye
K
Lee
Kuo-Hsiung
KH
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
D000970:Antineoplastic Agents; D003603:Cytotoxins; D013343:Styrenes; C052933:methyl-3-methoxy-4-hydroxystyryl ketone; D006034:Glycyrrhetinic Acid