Synthesis and antimicrobial properties of 3-aryl-1-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-yl)propanes as 'carba-analogues' of the N-arylmethyl-N-[(1,1'-biphenyl)-4-ylmethyl])-1H-imidazol-1-amines, a new class of antifungal agents.
A new series of 3-phenyl-1-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-yl)propane derivatives 2a-l (related to the antifungal bifonazole) was synthesized and tested for antimicrobial activity. A number of substituents on the phenyl ring were chosen to compare the relative biological properties with those of corresponding aza-analogues, previously described by us. The in vitro antifungal activities of the newly synthesized azoles were tested against several pathogenic fungi responsible for human disease. Test pathogens included representatives of yeasts (Candida albicans, Candida parapsilosis, Criptococcus neoformans), dermathophytes (Tricophyton verrucosum, Tricophyton rubrum, Microsporum gypseum) and moulds (Aspergillus fumigatus). Bifonazole and miconazole were used as reference drugs. Title compounds were prepared by alkylation of 1-biphenyl-4-yl-2-imidazol-1-yl-ethanone with the proper arylmethyl halide and subsequent reduction of corresponding ketones applying the Huang-Minlon modification of the Wolff-Kishner reaction.
Castellano
Sabrina
S
Dipartimento di Scienze Farmaceutiche, Università di Trieste, P.le Europa 1, 34127 Trieste, Italy.
Stefancich
Giorgio
G
Chillotti
Annalisa
A
Poni
Graziella
G
D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects; D001372:Aza Compounds / Q000737:chemistry / Q000494:pharmacology; D001555:Benzene Derivatives / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008825:Miconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008864:Microsporum / Q000187:drug effects; D011407:Propane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014249:Trichophyton / Q000187:drug effects; D015003:Yeasts / Q000187:drug effects
D000588:Amines; D000935:Antifungal Agents; D001372:Aza Compounds; D001555:Benzene Derivatives; D007093:Imidazoles; D008825:Miconazole; C036596:bifonazole; D011407:Propane