title: Synthesis and Antifungal Activity of Some 4,6-Dimethylisoxazolo[3,4- b]pyridin-3(1H)-one Derivatives.
abstract: BACKGROUND
  Cutaneous and invasive fungal infections are constant threats to human health that substantiate the need for the development of new efficacious and safe antimycotics.
  
  
  METHODS
  A series of N1-alkyl, N1-acyl and N1-sulfonyl derivatives of 4,6- dimethylisoxazolo[3,4-b]pyridin-3(1H)-one (1) were synthesized. The antimicrobial activities of title compounds against 21 pathogenic yeast-like fungal clinical isolates and 5 reference strains were evaluated by means of a broth microdilution method.
  
  
  RESULTS
  Among the compounds tested, the newly prepared N1-benzoyl (2m) and N1-(4-fluorobenzoyl) (2n) derivatives of 1 showed 81% and 95% inhibitory efficacy, respectively, against the clinical isolates, which were comparable to that of the reference drug fluconazole. The strains that exhibited the highest susceptibility to the compound 2n included Candida utilis (MIC < 6.2 μg/mL), C. parapsilosis (MIC in the range <6.2 - 12.5 μg/mL), Geotrichum candidum (MIC = 12.5 μg/mL) as well as C. lusitaniae and Rhodotorula mucilaginosa (MIC = 25 μg/mL).
  
  
  CONCLUSIONS
  In terms of MIC, compound 2n proved to be four times more active against the clinical isolates of Candida albicans and C. albicans ATCC 10231 standard strain than fluconazole, the widely prescribed antifungal agent for mucosal and systemic yeast infections (MIC = 50 vs 200 μg/mL).
authors.affiliation: Department of Organic Chemistry, Medical University of Gdansk, Al. Gen. J. Hallera 107, 80-416, Gdansk, Poland. js@gumed.edu.pl.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Saczewski
authors.forename: Joanna
authors.initials: J
authors.lastname: Fedorowicz
authors.forename: Anna
authors.initials: A
authors.lastname: Kedzia
authors.forename: Marta
authors.initials: M
authors.lastname: Ziolkowska-Klinkosz
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jalinska
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects; D005848:Geotrichum / Q000187:drug effects; D007555:Isoxazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D011728:Pyridones / Q000138:chemical synthesis / Q000494:pharmacology*; D012248:Rhodotorula / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D007555:Isoxazoles; D011728:Pyridones