title: Inhibitory effects of bufadienolides on interleukin-6 in MH-60 cells.
abstract: Derivatives of bufogenin isolated from the skin of the Chinese toad, Bufo bufo gargarizans Cantor ("Ch'an Su"), and several semisynthetic derivatives of 20beta,21beta-epoxy-resibufogenin (13) have been evaluated for interleukin-6 (IL-6) antagonistic activity due to their growth-inhibitory activities on IL-6-dependent MH-60 cells. Among the naturally derived compounds (1-17), 20S,21-epoxy-resibufogenin formate (1) showed potent inhibitory activity on the IL-6-dependent growth of MH-60 cells. Epoxide groups at both the C-14, C-15 and C-20, C-21 positions are required to exhibit this type of activity. Compounds acetylated at the C-16 position (7 and 9-11) showed a loss of activity. An oxo group at the C-3 position (8, 14, and 15) resulted in cytotoxicity for both cell lines. Stereochemistry is important for selectivity on suppression of IL-6 activity. Among the semisynthetic derivatives (18-25) of 13, compound 19, with an acetyl group introduced at the C-3 position in comparison to 13, demonstrated considerable growth inhibition of IL-6-dependent MH-60 cells.
authors.affiliation: The Kitasato Institute, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8642, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Enomoto
authors.forename: Mun-Chual
authors.initials: MC
authors.lastname: Rho
authors.forename: Kanki
authors.initials: K
authors.lastname: Komiyama
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D002018:Bufanolides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002023:Bufo bufo; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D051379:Mice; D015394:Molecular Structure; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured; D000093242:Interleukin-6 Inhibitors
chemical_list: D002018:Bufanolides; D000093242:Interleukin-6 Inhibitors; C022777:bufalin