Broad-spectrum antifungal activity of spirooxindolo-pyrrolidine tethered indole/imidazole hybrid heterocycles against fungal pathogens

被引：30
|
作者：
Bolous, Mina [1 ]
Arumugam, Natarajan [2 ]
Almansour, Abdulrahman, I [2 ]
Kumar, Raju Suresh [2 ]
Maruoka, Keiji [3 ]
Antharam, Vijay C. [4 ]
Thangamani, Shankar [5 ]
机构：
[1] Midwestern Univ, Coll Vet Med, 19555 N 59th Ave, Glendale, AZ 85308 USA
[2] King Saud Univ, Coll Sci, Dept Chem, POB 2455, Riyadh 11451, Saudi Arabia
[3] Kyoto Univ, Grad Sch Sci, Dept Chem, Sakyo Ku, Kyoto 6068502, Japan
[4] Methodist Univ, Sch Sci & Human Dev, Dept Chem, Fayetteville, NC USA
[5] Midwestern Univ, Coll Vet Med, Dept Pathol & Populat Med, 19555 N 59th Ave, Glendale, AZ 85308 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2019年 / 29卷 / 16期
关键词：
Antifungal agent; Toxicity; Spirooxindolo-pyrrolidine tethered indole/imidazole; 1,3-Dipolar cycloaddition; Ionic liquids; Candida; Cryptococcus; Fungi; Minimum inhibitory concentration (MIC); BLOOD-STREAM INFECTIONS; CANDIDA-ALBICANS; CANCER; SURVEILLANCE;
D O I：
10.1016/j.bmcl.2019.07.022
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Invasive fungal infections are one of the leading causes of nosocomial bloodstream infections with a limited treatment option. A series of derivatized spirooxindolo-pyrrolidine tethered indole and imidazole heterocyclic hybrids have been synthesized, and their antifungal activity against fungal strains were determined. Here we characterize the antifungal activity of a specific spirooxindolo-pyrrolidine hybrid, dubbed compound 9c, a spirooxindolo-pyrrolidine tethered imidazole synthesized with a 2-chloro and trifluoromethoxy substituent. The compound 9c exhibited no cytotoxicity against mammalian cell line at concentrations that inhibited fungal strains. Compound 9c also significantly inhibited the fungal hyphae and biofilm formation. Our results indicate that spirooxindolo-pyrrolidine heterocyclic hybrids potentially represent a broad class of chemical agents with promising antifungal potential.
引用
收藏
页码：2059 / 2063
页数：5
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