Anti- Toxoplasma gondii Activities and Structure-Activity Relationships of Novel Fluoroquinolones Related to Trovafloxacin
| Autor: | Jack S. Remington, Katherine E. Brighty, Fausto G. Araujo, Thomas D. Gootz, Anis A. Khan |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
medicine.drug_class
Biology Ring (chemistry) Microbiology Structure-Activity Relationship chemistry.chemical_compound Anti-Infective Agents medicine Animals Structure–activity relationship Pharmacology (medical) Naphthyridines Uracil IC50 Pharmacology Toxoplasma gondii Quinolone biology.organism_classification In vitro Trovafloxacin Infectious Diseases chemistry Susceptibility Toxoplasma Fluoroquinolones medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 43:1783-1787 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.43.7.1783 |
| Popis: | Eleven novel fluoroquinolones closely related to trovafloxacin were evaluated for their in vitro activity against Toxoplasma gondii , and their structure-activity relationships were examined. The 50% inhibitory concentration (IC 50 ) of trovafloxacin against T. gondii was 2.93 μM; the IC 50 of the 11 analogs ranged from 0.53 to 14.09 μM. Six analogs had IC 50 s lower than that of trovafloxacin. Examination of the structure-activity relationships of the compounds revealed that addition of a -CH 3 at C-5 of the 1,8-naphthyridone ring, at C-2 of the azabicyclohexane ring, or on the -NH 2 at the 6 position of the azabicyclohexane ring resulted in a four- to sixfold increase in activity. Moreover, replacement of 2,4-difluorophenyl by cyclopropyl at N-1 of the 1,8-naphthyridone ring increased activity twofold, and moving the -NH 2 one atom further away from the azabicyclohexane ring decreased activity. There was no difference between the naphthyridone and quinolone analogs. These results indicate that structure-activity studies of compounds related to drugs active against T. gondii may be useful in producing compounds with more potent activities against the parasite. |
| Databáze: | OpenAIRE |
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