Title: Selective in vitro and in vivo activities of 5-(2-haloalkyl)pyrimidine nucleoside analogs, particularly 5-(2-chloroethyl)-2'-deoxyuridine, against herpes simplex virus
Authors: De Clercq, Erik ×
Rosenwirth, B #
Issue Date: Aug-1985
Publisher: American Society for Microbiology (ASM)
Series Title: Antimicrobial Agents and Chemotherapy vol:28 issue:2 pages:246-51
Abstract: 5-(2-Chloroethyl)-2'-deoxyuridine (CEDU), 5-(3-chloropropyl)-2'-deoxyuridine (CPDU), and 5-(2-chloroethyl)-2'-deoxycytidine (CEDC) were evaluated for activity against herpes simplex virus type 1 (HSV-1) and HSV-2 in vitro. Their MICs for HSV-1 in primary rabbit kidney cell cultures were 0.15, 0.20, and 0.60 micrograms/ml, respectively; their MICs for HSV-2 were about 10-fold higher. When tested in parallel, the reference compounds 5-ethyl-2'-deoxyuridine, 5-iodo-2'-deoxyuridine, acyclovir, and (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) gave MICs of 0.20, 0.18, 0.04, and 0.015 micrograms/ml, respectively. The antiviral indexes of CEDU, CPDU, and CEDC, as determined by the ratio of the minimum toxic dose for the normal host cell to the minimum inhibitory dose for HSV-1, were about 2,000, 100, and greater than or equal to 400, respectively. The three 5-(2-haloalkyl)pyrimidine derivatives were further evaluated for their antiviral effects in vivo. In hairless mice, CEDU suppressed the development of cutaneous HSV-1 lesions, and associated mortality, when applied topically at a concentration as low as 0.1%. For the treatment of systemic HSV-1 infection in Naval Medical Research Institute mice, a single oral dose per day of 5 mg of CEDU per kg achieved a significant reduction in the mortality rate. Against HSV-1 encephalitis, CEDU exerted a significant protective effect at a dosage of 50 mg/kg per day when administered intraperitoneally. CEDU was effective against systemic HSV-1 infection and HSV-1 encephalitis in mice at a 5- to 15-fold-lower dose than either BVDU or acyclovir. When given orally, CPDU and CEDC were considerably less active than CEDU against systemic HSV-1 infection.
ISSN: 0066-4804
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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