title: Phosphonylmethoxyalkylpurines and -pyrimidines as inhibitors of African swine fever virus replication in vitro.
abstract: Several phosphonylmethoxyalkylpurine and -pyrimidine derivatives related to (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA] and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) were evaluated as inhibitors of African swine fever virus (ASFV) replication in Vero cells. (S)-HPMPA has previously been shown to inhibit ASFV replication at a minimum inhibitory concentration (MIC) of 0.01 microgram/ml with a selectivity index of 15000. Of the new compounds tested, the following emerged as the most potent and selective inhibitors of ASFV replication: the cyclic phosphonate of (S)-HPMPA [(S)-cHPMPA] with an MIC of 0.2 microgram/ml and a selectivity index of 2500, the 2,6-diaminopurine analogue of (S)-HPMPA [(S)-HPMPDAP] with an MIC of 0.5 microgram/ml and a selectivity index of 1400, and the cytosine [(S)-HPMPC] and guanine [(RS)-HPMPG] analogues with an MIC of 1 microgram/ml and a selectivity index of 600-700.
authors.affiliation: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Gil-Fernández
authors.forename: D
authors.initials: D
authors.lastname: García-Villalón
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: I
authors.initials: I
authors.lastname: Rosenberg
authors.forename: A
authors.initials: A
authors.lastname: Holý
mesh_terms: D000358:African Swine Fever Virus / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000998:Antiviral Agents; D002470:Cell Survival / Q000187:drug effects; D007497:Iridoviridae / Q000187:drug effects*; D009943:Organophosphorus Compounds / Q000494:pharmacology* / Q000633:toxicity; D011687:Purines / Q000494:pharmacology* / Q000633:toxicity; D011743:Pyrimidines / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D009943:Organophosphorus Compounds; D011687:Purines; D011743:Pyrimidines