<i>In vitro</i>Activity of Acyclic Nucleoside Phosphonate Derivatives against Feline Immunodeficiency Virus in Crandell Feline Kidney Cells and Feline Peripheral Blood Lymphocytes

Several novel fluorinated acyclic nucleoside phosphonates [i.e. 9-(3-fluoro-2-phosphonylmethoxy propyl)adenine (FPMPA) and 9-(3-fluoro-2-phosphonylmethoxypropyl)-2,6-diaminopurine (FPMPDAP)] were evaluated for their inhibitory effect against feline immunodeficiency virus (FIV) replication in Crandell feline kidney (CrFK) cells and feline peripheral blood lymphocytes (PBL) in vitro. Whereas 3-azido-3-deoxythymidine (AZT) was not able to achieve complete suppression of viral antigen expression and reverse transcriptase activity in the FIV-infected cell culture supernatants at 25 μM, FPMPA, FPMPDAP, and the 9-(2-phosphonylmethoxyethyl)purine derivatives PMEA and PMEDAP fully protected FIV-infected cells at μM. Both FPMPA and FPMPDAP were endowed with a higher antiviral potency and/or therapeutic selectivity than PMEA and PMEDAP in inhibiting FIV infection, mainly due to a markedly lower toxicity for the cell cultures.