In vitro and in vivo activities of SCH 42427, the active enantiomer of the antifungal agent SCH 39304
| Autor: | Christine Norris, David Loebenberg, Raulo Parmegiani, Taisa Yarosh-Tomaine, F. Menzel, Roberta S. Hare, George H. Miller, B Antonacci, Eugene L. Moss, Anthony Cacciapuoti |
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| Rok vydání: | 1992 |
| Předmět: |
Male
Antifungal Agents Guinea Pigs Triazole Aspergillus flavus Microbial Sensitivity Tests Pharmacology Biology Mice chemistry.chemical_compound Trichophyton In vivo Cricetinae polycyclic compounds Animals Aspergillosis Dermatomycoses heterocyclic compounds Pharmacology (medical) Candidiasis Vulvovaginal ED50 Mesocricetus organic chemicals Candidiasis Fungi Rats Inbred Strains Stereoisomerism Triazoles biology.organism_classification Effective dose (pharmacology) In vitro Corpus albicans Rats carbohydrates (lipids) Infectious Diseases nervous system chemistry Female Enantiomer Research Article |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 36:498-501 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.36.2.498 |
| Popis: | SCH 39304, a new triazole antifungal agent, is a 50:50 racemic mixture of two enantiomers, SCH 42427 and SCH 42426. The activities of these three compounds were compared in a series of in vitro and in vivo experiments. SCH 42427 was twofold more active in vitro against a variety of yeasts and dermatophytes than SCH 39304, while SCH 42426 was inactive (MICs greater than 64 micrograms/ml). In a systemic Candida albicans infection in mice, SCH 42427 administered orally (p.o.) (50% protective dose [PD50], 0.17 mg/kg of body weight; 50% effective dose, [ED50], 0.47 mg/kg) had greater efficacy than SCH 39304 (PD50, 0.21 mg/kg; ED50, 0.62 mg/kg) and SCH 42426 (greater than 100 mg/kg for PD50 and ED50). In a pulmonary Aspergillus flavus infection in mice, SCH 42427 p.o. (PD50, 13 mg/kg) was also more effective than SCH 39304 (18 mg/kg) and SCH 42426 (greater than 250 mg/kg). In a C. albicans vaginal infection in hamsters, SCH 42427 p.o. (ED50, 3.5 mg/kg) was more active than SCH 39304 (8.5 mg/kg) and SCH 42426 (320 mg/kg). Following topical administration, against a Trichophyton mentagrophytes infection in guinea pigs, SCH 42427 was about 2-fold more active than SCH 39304 and about 100-fold more active than SCH 42426. These and other results indicated that SCH 42427 is the active enantiomer, responsible for all the antifungal activity observed with SCH 39304. |
| Databáze: | OpenAIRE |
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