Influence of vehicle on topical efficacy of 2-acetylpyridine thiosemicarbazone and related derivatives on in vivo type 2 herpes simplex virus infections.

Abstract

2-Acetylpyridine semicarbazone (APSC), 2-acetylpyridine thiosemicarbazone (APTSC) and 2-acetylpyridine-4-methyl-3-thiosemicarbazonoe (APMTSC) were evaluated against type-2 herpes simplex virus (HSV-2)-induced genitalis and encephalitis in mice and guinea pigs. The antiviral activity of these compounds was compared with that of acyclovir. With 1,3-butanediol as a topical treatment vehicle, 1% APSC and APTSC showed significant activity against the genital infection in mice, as evidenced by increased survivors and decreased severity of vaginal lesions. Reduced titers of virus recovered from the lesions were also observed with APTSC treatments. Eight different commercially available vehicles were compared to determine in which topically administered 1% APTSC would be most efficacious against the vaginal disease induced in mice. Significant results were observed with Squibb cream base, Eucerin base, and K-Y jelly; these effects were essentially equivalent to using 1,3-butanediol Unibase, Aquaphor, polyethylene glycol, polyvinyl alcohol and petrolatum were less effective as carrier vehicles. The herpesvirus genital infection in guinea pigs was treated with 1% APMTSC and APTSC comparing Squibb cream, Eucerin and K-Y jelly bases; while neither compound exerted striking effects against this infection in any vehicle, 1% APMTSC in Squibb cream was effective in increasing mean survival time and reducing lesion score and titers of recoverable virus. In this experiment, treatments with 1 and 5% acyclovir in polyethylene glycol base were effective in reducing titers of virus from the vaginal area. Orally administered APTSC (12.5, 25, 50 mg/kg/day given twice daily for 7 days) caused moderate prevention of death of mice infected intraperitoneally with HSV-2; subcutaneous injection of the compound was markedly effective with efficacy comparable to that of acyclovir at 120 mg/kg/day.

• Authors: R W Sidwell, J H Huffman, T W Schafer, C Shipman
• Journal: Chemotherapy (Chemotherapy) Vol. 36 Issue 1 Pg. 58-69 ( 1990) ISSN: 0009-3157 [Print] Switzerland
• PMID: 2155092 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Butylene Glycols
• Pharmaceutical Vehicles
• Semicarbazones
• Thiosemicarbazones
• 2-acetylpyridine semicarbazone
• 1,3-butylene glycol
• 2-acetylpyridine thiosemicarbazone
• 2-acetylpyridine-4-methyl-3-thiosemicarbazone

Topics

• Administration, Intravaginal
• Administration, Topical
• Animals
• Butylene Glycols (administration & dosage)
• Female
• Genital Diseases, Female (drug therapy, microbiology)
• Guinea Pigs
• Herpes Simplex (drug therapy, microbiology)
• Mice
• Pharmaceutical Vehicles
• Semicarbazones (administration & dosage, pharmacology)
• Simplexvirus (drug effects)
• Thiosemicarbazones (administration & dosage, pharmacology)