TY - JOUR
T1 - A-ring modified betulinic acid derivatives as potent cancer preventive agents
AU - Hung, Hsin Yi
AU - Nakagawa-Goto, Kyoko
AU - Tokuda, Harukuni
AU - Iida, Akira
AU - Suzuki, Nobutaka
AU - Bori, Ibrahim D.
AU - Qian, Keduo
AU - Lee, Kuo Hsiung
N1 - Funding Information:
This work was supported in part by NIH Grant CA177584-01 from the National Cancer Institute and AI-33066-22 from the National Institute of Allergy and Infectious Diseases awarded to K.-H. Lee.
PY - 2014/2/1
Y1 - 2014/2/1
N2 - Ten new 3,4-seco betulinic acid (BA) derivatives were designed and synthesized. Among them, compounds 7-15 exhibited enhanced chemopreventive ability in an in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA) induced Epstein-Barr virus early antigen (EBV-EA) activation assay in Raji cells. Specifically, analogs with a free C-28 carboxylic acid, including 7, 8, 11, and 13, inhibited EBV-EA activation significantly. The most potent compound 8 displayed 100% inhibition at 1 × 103 mol ratio/TPA and 73.4%, 35.9%, and 8.4% inhibition at 5 × 102, 1 × 10 2, and 1 × 10 mol ratio/TPA, respectively, comparable with curcumin at high concentration and better than curcumin at low concentration. The potent chemopreventive activity of novel seco A-ring BAs (8 and 11) was further confirmed in an in vivo mouse skin carcinogenesis assay.
AB - Ten new 3,4-seco betulinic acid (BA) derivatives were designed and synthesized. Among them, compounds 7-15 exhibited enhanced chemopreventive ability in an in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA) induced Epstein-Barr virus early antigen (EBV-EA) activation assay in Raji cells. Specifically, analogs with a free C-28 carboxylic acid, including 7, 8, 11, and 13, inhibited EBV-EA activation significantly. The most potent compound 8 displayed 100% inhibition at 1 × 103 mol ratio/TPA and 73.4%, 35.9%, and 8.4% inhibition at 5 × 102, 1 × 10 2, and 1 × 10 mol ratio/TPA, respectively, comparable with curcumin at high concentration and better than curcumin at low concentration. The potent chemopreventive activity of novel seco A-ring BAs (8 and 11) was further confirmed in an in vivo mouse skin carcinogenesis assay.
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U2 - 10.1016/j.bmcl.2013.12.041
DO - 10.1016/j.bmcl.2013.12.041
M3 - Article
C2 - 24411124
AN - SCOPUS:84893704405
SN - 0960-894X
VL - 24
SP - 1005
EP - 1008
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 3
ER -