Antifungal Activity of Gepinacin Scaffold Glycosylphosphatidylinositol Anchor Biosynthesis Inhibitors with Improved Metabolic Stability. Academic Article uri icon

Overview

abstract

  • The glycosylphosphatidylinositol anchor biosynthesis inhibitor gepinacin demonstrates broad-spectrum antifungal activity and negligible mammalian toxicity in culture but is metabolically labile. The stability and bioactivity of 39 analogs were tested in vitro to identify LCUT-8, a stabilized lead with increased potency and promising single-dose pharmacokinetics. Unfortunately, no antifungal activity was seen at the maximum dosing achievable in a neutropenic rabbit model. Nevertheless, structure-activity relationships identified here suggest strategies to further improve compound potency, solubility, and stability.

publication date

  • September 21, 2020

Research

keywords

  • Antifungal Agents
  • Glycosylphosphatidylinositols

Identity

PubMed Central ID

  • PMC7508603

Scopus Document Identifier

  • 85091470055

Digital Object Identifier (DOI)

  • 10.1128/AAC.46.6.1857-1869.2002

PubMed ID

  • 32661007

Additional Document Info

volume

  • 64

issue

  • 10