title: Synthetic derivatives of osthole for the prevention of hepatitis.
abstract: Prevention of hepatitis is a worldwide issue. For most patients with liver disease, hepatoprotective drugs are required. But there are only a few hepatoprotective drugs available. Osthole is a coumarin compound and protects the liver from hepatitis by preventing the development of apoptosis. However, osthole exhibits low water solubility, and some structural modifications are required for sufficient hepatoprotection upon oral administration. We synthesized 28 osthole derivatives, and then studied their effects by using mice concanavalin A (Con A) -induced hepatitis. The osthole derivatives No.1, 9 and 19 showed stronger inhibition of Con A-induced elevation of plasma alanine aminotransferase (ALT). Oral administration of osthole at the dose of 100 mg/kg (n=10) inhibited 38.0% of the Con A-induced elevation of plasma ALT. In contrast, oral administration of Nos. 1, 9 and 19 at the dose of 100 mg/kg (n=5) caused 68.7%, 62.5% and 88.3% inhibition of the Con A-induced elevation of plasma ALT, respectively. These synthetic osthole derivatives could contribute to the development of hepatoprotective drugs effective for various types of liver diseases on oral administration.
authors.affiliation: Research Laboratories, Nippon Chemiphar Co., Ltd, Misato, Saitama 341-0005, Japan. t-okamoto@chemiphar.co.jp
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Okamoto
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yoshida
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D003208:Concanavalin A; D003374:Coumarins / Q000138:chemical synthesis* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D007202:Indicators and Reagents; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D003374:Coumarins; D007202:Indicators and Reagents; D003208:Concanavalin A; D000410:Alanine Transaminase; C046627:osthol