Antifungal Activity of Gepinacin Scaffold Glycosylphosphatidylinositol Anchor Biosynthesis Inhibitors with Improved Metabolic Stability.
Antimicrob Agents Chemother
; 64(10)2020 09 21.
Article
en En
| MEDLINE
| ID: mdl-32661007
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Glicosilfosfatidilinositoles
/
Antifúngicos
Límite:
Animals
Idioma:
En
Año:
2020
Tipo del documento:
Article