Discovery of novel indazole-linked triazoles as antifungal agents.
The in vitro and in vivo activities of a series of (2R,3R)-2-(2,4-difluorophenyl)-3-(substituted indazol-1-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol as potential antifungal agents are described. In particular, the analog 12j having 5-bromo substitution on the indazole ring exhibited significant antifungal activity against a variety of fungal cultures (Candida spp. and Aspergillus spp.). In addition, oral administration of 12j showed its excellent efficacy against Candida albicans in a murine infection model and the significantly improved survival rates of the infected mice.
Park
Joon Seok
JS
College of Pharmacy, Seoul National University, San 56-1 Shinrim-Dong, Kwanak-Gu, Seoul 151-742, Republic of Korea.
Yu
Kyung A
KA
Kang
Tae Hee
TH
Kim
Sunghoon
S
Suh
Young-Ger
YG
D000284:Administration, Oral; D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D001230:Aspergillus / Q000187:drug effects* / Q000254:growth & development; D002175:Candida / Q000187:drug effects* / Q000254:growth & development; D004195:Disease Models, Animal; D007191:Indazoles / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008826:Microbial Sensitivity Tests; D051381:Rats; D013237:Stereoisomerism; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use
D000935:Antifungal Agents; D007191:Indazoles; D014230:Triazoles