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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 IC50 values of 0.0048, 0.0044, and 0.014mM, respectively, HBeAg with IC50 values of 0.011, 0.012, and 0.018mM, respectively, and remarkable selective index values SIHBsAg >333, SIHBeAg >145; SIHBsAg =209, SIHBeAg =77; and SIHBsAg >200, SIHBeAg >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 1.63h and oral bioavailability (F) of 40.9%. [Copyright &y& Elsevier]

Abstract: Chemical modifications were performed on hydroxyl groups at C-11,23,24,25 positions and C-13(17) double bond of alisol A for structure–activity relationship study. Forty-one derivatives of alisol A were synthesized and assayed for their in vitro anti-hepatitis B virus (HBV) activities and cytotoxicities. Of them, 14 compounds were active against HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) secretion in HepG 2.2.15 cells, and the most promising compound 25 exhibited high activities against secretion of HBsAg (IC50 =0.028mM), HBeAg (IC50 =0.027mM) and remarkable selective indices (SIHBsAg >90, SIHBeAg >93). [Copyright &y& Elsevier]

Abstract: A series of 1-aryl-6,7-dihydroxyl(methoxy)-1,2,3,4-tetrahydroisoquinolines (compounds 1–36) were synthesized via Pictet–Spengler cyclization. All the synthesized compounds were assayed for activities against HIV-1IIIB in C8166 cell cultures by MTT method for the first time. The results of the anti-HIV screening revealed that 6,7-dihydroxytetrahydroisoquinolines possessed higher selective index than 6,7-dimethoxyl analogs due to the significantly decreased cytotoxicities. Compounds 6, 24, and 36 showed potent anti-HIV activities with EC50 values of 8.2, 4.6, and 5.3μM respectively, and the cytotoxicities (CC50) of these three compounds were 784.3, 727.3, and 687.3μM, which resulted in SI values larger than 95, 159, and 130 respectively. [Copyright &y& Elsevier]