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Titolo:
ACYCLIC PHOSPHONOMETHYLETHER NUCLEOSIDE INHIBITORS OF RESPIRATORY VIRUSES
Autore:
BARNARD DL; BISCHOFBERGER N; KIM CU; HUFFMAN JH; SIDWELL RW; DOUGHERTY JR; LEW W; WILLIAMS MA; YANG W;
Indirizzi:
UTAH STATE UNIV,INST ANTIVIRAL RES LOGAN UT 84322 GILEAD SCI INC FOSTER CITY CA 94404
Titolo Testata:
Antiviral chemistry & chemotherapy
fascicolo: 3, volume: 8, anno: 1997,
pagine: 223 - 233
SICI:
0956-3202(1997)8:3<223:APNIOR>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHOSPHONATE NUCLEOTIDE ANALOGS; INTERFERON INDUCTION; 2'-NOR-CYCLIC GMP; PMEA; INVITRO; GENES; 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE; REPLICATION; ACYCLOVIR; STRAINS;
Keywords:
ACYCLIC; PHOSPHONOMETHYLETHER; NUCLEOSIDE; ADENOVIRUS; MEASLES VIRUS; PARAINFLUENZA VIRUS 3;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
30
Recensione:
Indirizzi per estratti:
Citazione:
D.L. Barnard et al., "ACYCLIC PHOSPHONOMETHYLETHER NUCLEOSIDE INHIBITORS OF RESPIRATORY VIRUSES", Antiviral chemistry & chemotherapy, 8(3), 1997, pp. 223-233

Abstract

A series of acyclic phosphonomethylether nucleosides were synthesizedand then evaluated for inhibitory activity against respiratory viruses of clinical significance using CPE inhibition, neutral red uptake and virus yield reduction assays. Of the 20 compounds synthesized, none significantly inhibited influenza A or B viruses or respiratory syncytial virus strains A2, Long or 18537; the selective indices (SI) were less than 10. A new compound, GS-2128 (2R, 2,5-dihydro-5-(phosphonomethoxy)2-furanyl]adenine; D4API), selectively inhibited adenovirus 5 (SI>10) as did GS-0577 (9-(3-hydroxy-2-phosphonylmethoxypropyl)-adenine; HPMPA) and GS-0504 [(S)-1 -[3-hydroxy-2-(phosphonylmethoxypropyl)-cytosine; HPMPC]. The 50% effective concentrations (EC50) ranged from 8-100mu g ml(-1) and 50% cell inhibitory concentrations (CC50) from 40-1000)19 mu g ml(-1). All three compounds were also found to be active against laboratory strains and clinical isolates of adenovirus types 1, 2, 8 and 41 with EC50 values ranging from 0.2 to 10 mu g ml(-1) Two compounds, GS-438 (9-(2-phosphonylmethoxyethyl)guanine, PMEG) and GS-2542(9-[3-phosphonomethoxy)methoxymethyl]guanine) inhibited parainfluenzavirus 3 strain C243, with SI of 52 and >333, respectively. PMEG also inhibited measles virus strains CC, Halonen and Chicago with EC50 Values ranging from 0.03-9 mu g ml(-1). These data suggest that these compounds should be considered for possible development as therapeutic agents for respiratory virus infections.

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Documento generato il 04/07/20 alle ore 20:59:08