College of Veterinary Medicine, Midwestern University, 19555 N. 59th Ave., Glendale, AZ 85308, United States.
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Bioorg Med Chem Lett. 2019 Aug 15;29(16):2059-2063. doi: 10.1016/j.bmcl.2019.07.022. Epub 2019 Jul 13.
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.
侵袭性真菌感染是医院获得性血流感染的主要原因之一，其治疗选择有限。我们合成了一系列衍生的螺环[吲哚啉-吡咯烷]连接的吲哚和咪唑杂环杂合体，并测定了它们对真菌株的抗真菌活性。在这里，我们描述了一种特定的螺环[吲哚啉-吡咯烷]杂合体的抗真菌活性，该杂合体被称为化合物 9c，是一种带有 2-氯和三氟甲氧基取代基的螺环[吲哚啉-吡咯烷]连接的咪唑。在抑制真菌株的浓度下，化合物 9c 对哺乳动物细胞系没有细胞毒性。化合物 9c 还显著抑制真菌菌丝和生物膜的形成。我们的结果表明，螺环[吲哚啉-吡咯烷]杂环杂合体可能代表一类具有广阔应用前景的抗真菌化学试剂。
