title: Synthesis and antimicrobial activity of new 3-(1-R-3(5)-methyl-4-nitroso-1H-5(3)-pyrazolyl)-5-methylisoxazoles.
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.
authors.affiliation: Dipartimento Farmacochimico Tossicologico e Biologico, Università degli Studi, Palermo, Italy. eaiello@unipa.it
authors.forename: E
authors.initials: E
authors.lastname: Aiello
authors.forename: S
authors.initials: S
authors.lastname: Aiello
authors.forename: F
authors.initials: F
authors.lastname: Mingoia
authors.forename: A
authors.initials: A
authors.lastname: Bacchi
authors.forename: G
authors.initials: G
authors.lastname: Pelizzi
authors.forename: C
authors.initials: C
authors.lastname: Musiu
authors.forename: M G
authors.initials: MG
authors.lastname: Setzu
authors.forename: A
authors.initials: A
authors.lastname: Pani
authors.forename: P
authors.initials: P
authors.lastname: La Colla
authors.forename: M E
authors.initials: ME
authors.lastname: Marongiu
mesh_terms: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003455:Cryptococcus neoformans / Q000187:drug effects; D005658:Fungi / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000935:Antifungal Agents; D007555:Isoxazoles