Anti-HBV agents. Part 3: preliminary structure-activity relationships of tetra-acylalisol A derivatives as potent hepatitis B virus inhibitors.
Bioorg Med Chem Lett
; 19(23): 6659-65, 2009 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-19853440
ABSTRACT
Thirty-two tetra-acylated derivatives of alisol A were synthesized and evaluated for their anti-hepatitis B virus (HBV) activities and cytotoxicities in vitro. Among the series of alisol A derivatives examined, five analogues were active against HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) secretion in HepG 2.2.15 cells. These results also provide interesting structure-activity relationships of tetra-acylalisol A derivatives. Compounds tetra-acetyl alisol A (A1), tetra-methoxyacetyl alisol A (A23), and tetra-ethoxyacetyl alisol A (A24) exhibited high activities against secretion of HBsAg with IC(50) values of 0.0048, 0.0044, and 0.014 mM, respectively, HBeAg with IC(50) values of 0.011, 0.012, and 0.018 mM, respectively, and remarkable selective index values SI(HBsAg)>333, SI(HBeAg)>145; SI(HBsAg)=209, SI(HBeAg)=77; and SI(HBsAg)>200, SI(HBeAg)>156, respectively. Additional studies in rats showed that compound A1 has favorable pharmacokinetic prosperities for further development purpose, with elimination half-time (t(1/2)) of 1.63 h and oral bioavailability (F) of 40.9%.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Vírus da Hepatite B
/
Colestenonas
Idioma:
En
Revista:
Bioorg Med Chem Lett
Ano de publicação:
2009
Tipo de documento:
Article