title: Supramolecular high-aspect ratio assemblies with strong antifungal activity.
abstract: Efficient and pathogen-specific antifungal agents are required to mitigate drug resistance problems. Here we present cationic small molecules that exhibit excellent microbial selectivity with minimal host toxicity. Unlike typical cationic polymers possessing molecular weight distributions, these compounds have an absolute molecular weight aiding in isolation and characterization. However, their specific molecular recognition motif (terephthalamide-bisurea) facilitates spontaneous supramolecular self-assembly manifesting in several polymer-like properties. Computational modelling of the terephthalamide-bisurea structures predicts zig-zag or bent arrangements where distal benzyl urea groups stabilize the high-aspect ratio aqueous supramolecular assemblies. These nanostructures are confirmed by transmission electron microscopy and atomic force microscopy. Antifungal activity against drug-sensitive and drug-resistant strains with in vitro and in vivo biocompatibility is observed. Additionally, despite repeated sub-lethal exposures, drug resistance is not induced. Comparison with clinically used amphotericin B shows similar antifungal behaviour without any significant toxicity in a C. albicans biofilm-induced mouse keratitis model.
authors: 1] IBM Almaden Research Center, 650 Harry Road, San Jose, California 95120, USA [2] Department of Polymer Science and Engineering, Yamagata University, Yonezawa, Yamagata 992-8510, Japan [3].
authors: Kazuki
authors: K
authors: Fukushima
authors: Shaoqiong
authors: S
authors: Liu
authors: Hong
authors: H
authors: Wu
authors: Amanda C
authors: AC
authors: Engler
authors: Daniel J
authors: DJ
authors: Coady
authors: Hareem
authors: H
authors: Maune
authors: Jed
authors: J
authors: Pitera
authors: Alshakim
authors: A
authors: Nelson
authors: Nikken
authors: N
authors: Wiradharma
authors: Shrinivas
authors: S
authors: Venkataraman
authors: Yuan
authors: Y
authors: Huang
authors: Weimin
authors: W
authors: Fan
authors: Jackie Y
authors: JY
authors: Ying
authors: Yi Yan
authors: YY
authors: Yang
authors: James L
authors: JL
authors: Hedrick
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects / Q000502:physiology; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D011108:Polymers