Anti-Candida albicans properties of novel benzoxazine analogues.
We previously reported that azole 1,4-benzothiazine derivatives have appreciable anti-Candida activity. In this study, we synthesized 1,4-benzoxazine analogues and examined their possible antifungal activity to further analyze the structure-activity relationships. Results of in vitro and in vivo experiments showed that 1,4-benzoxazine analogues show appreciable antifungal activity. In particular, they have significant capability to cure mice systemically infected with a lethal challenge of Candida albicans, as indicated by increased survival time paralleling reduction of colony forming units. Moreover, 1,4-benzoxazine derivatives also showed immunomodulating activity, as indicated by a significant increase of interleukin-12 and interferon-gamma production by splenocytes and reinforcement of a T helper type 1 protective immune response to C. albicans. In conclusion, the results demonstrate that replacement of sulfur by oxygen may improve immune response against C. albicans infection.
Fringuelli
Renata
R
Department of Drug Chemistry and Technology, University of Perugia, Via del Liceo 1, 06123, Perugia, Italy. fringuel@unipg.it
Pietrella
Donatella
D
Schiaffella
Fausto
F
Guarraci
Alessia
A
Perito
Stefano
S
Bistoni
Francesco
F
Vecchiarelli
Anna
A
D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002176:Candida albicans / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000382:microbiology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010078:Oxazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000935:Antifungal Agents; D010078:Oxazines