Antiviral effects of three novel derivatives of adefovir on the replication of hepatitis B virus

Abstract

Nucleoside/tide analogs are now widely used for treatment of chronic hepatitis B (CHB). However, available nucleoside/tide analogs for treatment of CHB usually have limited therapeutic effect and potential adverse effects on CHB patients. We evaluated the anti-HBV effects of three novel derivatives (compounds 1, 4, and 8) of adefovir on the replication of hepatitis B virus (HBV) and determined their cytotoxicity. The effects of those compounds on the replication of human HBV in the HepG2 2.2.15 cell line and duck HBV in infected ducks were characterized by measuring the extracellular and intracellular HBV DNA using the quantitative real-time PCR and Southern blot assays. Their cytotoxicities against HepG2 cells were evaluated by MTT and measuring the contents of mitochondrial DNA using the dot blot assay. We found that all of the compounds inhibited the production of HBV in a dose-dependent manner, similar to that of adefovir dipivoxil. Furthermore, treatment with any of the compounds reduced significantly the replication of DHBV in ducks, accompanied by a significant reduction of inflammation in the livers, and the compound 1 appeared to be a fast-acting and long-lasting anti-DHBV reagent. Importantly, all of the compounds showed little cytotoxicity against HepG2 cells, even at a concentration of 1 mM. Collectively, those novel derivatives of adefovir had potent anti-HBV activity with little adverse effect and may be therapeutic candidates for potential clinical studies.

Direct Synthesis of Phosphonates and α-Amino-phosphonates from 1,3-Benzoxazines

“…The α-aminophosphonic acids are probably the most important analogues of α-amino acids attributed to their structural analogy obtained by isosteric substitution of planar carboxylic acid (CO 2 H) by tetrahedral phosphonic acid (PO 3 H 2 ) [1,2,3]. This kind of compounds have been widely studied and used in agriculture, industry and medicinal chemistry [4,5,6,7,8,9].…”

Palladium-Catalyzed α-Arylation of Benzylic Phosphonates

“…Phosphonates and their derivatives are a class of organophosphorus compounds that exhibit a wide range of applications in medicinal 1 and agricultural chemistry. 2 They are also flame retardants, metal extractants, 3 and reagents in the Horner–Wadsworth–Emmons (HWE) reaction.…”