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Novel carboline derivatives as potent antifungal lead compounds: design, synthesis, and biological evaluation. 2014
Shengzheng Wang, and
Yan Wang, and
Wei Liu, and
Na Liu, and
Yongqiang Zhang, and
Guoqiang Dong, and
Yang Liu, and
Zhengang Li, and
Xiaomeng He, and
Zhenyuan Miao, and
Jianzhong Yao, and
Jian Li, and
Wannian Zhang, and
Chunquan Sheng
School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, People's Republic of China.
A series of novel antifungal carboline derivatives was designed and synthesized, which showed broad-spectrum antifungal activity. Particularly, compound C38 showed comparable in vitro antifungal activity to fluconazole without toxicity to human embryonic lung cells. It also exhibited good fungicidal activity against both fluconazole-sensitive and -resistant Candida albicans cells and had potent inhibition activity against Candida albicans biofilm formation and hyphal growth. Moreover, C38 showed good synergistic antifungal activity in combination with fluconazole (FLC) against FLC-resistant Candida species. Preliminary mechanism studies revealed that C38 might act by inhibiting the synthesis of fungal cell wall.
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