Synthesis of Feruloyl- myo-insitol derivatives and their inhibitory effects on phorbol ester-induced superoxide generation and esptein–barr virus activation

• Published in: Bioorganic & medicinal chemistry 2002-06, Vol.10 (6), p.1855-1863
• Main Authors: Hosoda, Asao, Nomura, Eisaku, Murakami, Akira, Koshimizu, Koichi, Ohigashi, Hajime, Mizuno, Kazuhiko, Taniguchi, Hisaji
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Cell Line; Chemical agents; Herpesvirus 4, Human - drug effects; Herpesvirus 4, Human - growth & development; Herpesvirus 4, Human - physiology; HL-60 Cells; Humans; Inositol - analogs & derivatives; Inositol - chemical synthesis; Inositol - chemistry; Inositol - pharmacology; Medical sciences; Models, Molecular; Molecular Conformation; Molecular Structure; NADPH Oxidases - metabolism; Phorbol Esters - pharmacology; Stereoisomerism; Structure-Activity Relationship; Superoxides - metabolism; Tumors; Virus Activation - drug effects
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/S0968-0896(02)00010-X

We prepared 14 feruloyl- myo-inositol derivatives, and evaluated the relationships between their stereostructure and inhibitory activity toward the 12- O-tetradecanoylphorbol-13-acetate (TPA)-induced superoxide (O 2 −) generation. And further, their suppressive effect on the TPA-induced Epstein–Barr virus (EBV) activation was examined in order to estimate their anti-carcinogenic potentials. Among the derivatives tested, 1,6- O-bis[3-(4′-hydroxy-3′-methoxyphenyl)-2-propenoyl]- myo-inositol ( 6b) showed an excellent suppressive activity on the O 2 − generation at a concentration of 20 μM. For the suppressive effects on the EBV activation, 2,4,6- O-tris[3-(4′-hydroxy-3′-methoxyphenyl)-2-propenoyl]- myo-inositol 1,3,5-orthoformate ( 9b) showed the highest activity at a concentration of 100 μM among the derivatives tested. These results suggest that the inhibitory potencies of feruloyl- myo-inositol derivatives depend on the stereostructure of molecules rather than the hydrophobicity of molecules. We prepared 14 feruloyl- myo-inositol derivatives, and examined their structure–activity relationship of the inhibitory activity toward the TPA-induced O 2 − generation and the EBV activation.