Author/Authors :
Enrico Aiello، نويسنده , , Stefania Aiello، نويسنده , , Francesco Mingoia، نويسنده , , Alessia Bacchi، نويسنده , , Giancarlo Pelizzi، نويسنده , , Chiara Musiu، نويسنده , , Maria Giovanna Setzu، نويسنده , , Alessandra Pani، نويسنده , , Paolo La Colla، نويسنده , , Maria Elena Marongiu، نويسنده ,
Abstract :
A number of new 3-(1-R-3(5)-methyl-4-nitroso-1H-5(3)-pyrazolyl)-5-methylisoxazoles 6a–g (7b–f) were synthesized and tested for antibacterial and antifungal activity. Some of these compounds displayed antifungal activity at non-cytotoxic concentrations. Derivative 6c was 9 times more potent in vitro than miconazole and 20 times more selective against C. neoformans. 6c was also 8- and 125-fold more potent than amphotericin B and fluconazole, respectively. None of the compounds was active against bacteria. Preliminary structure–activity relationship (SAR) studies showed that the NO group at position 4 of the pyrazole ring is essential for the activity. Lipophilicity of the pyrazole moiety, N-alkyl chain length and planarity of the two heterocyclic rings appear to play a decisive role in modulating cytotoxicity and antifungal activity.
