Antifungal Activity of 6-substituted Amiloride and Hexamethylene Amiloride (HMA) Analogs

Overview

Journal Front Cell Infect Microbiol

Specialties Cell Biology
Infectious Diseases
Microbiology

Date 2023 Mar 16

PMID 36923593

Authors

Kiem Vu

Benjamin J Buckley

Richard S Bujaroski

Eduardo Blumwald

Michael J Kelso

Angie Gelli

Affiliations

Soon will be listed here.

Abstract

Fungal infections have become an increasing threat as a result of growing numbers of susceptible hosts and diminishing effectiveness of antifungal drugs due to multi-drug resistance. This reality underscores the need to develop novel drugs with unique mechanisms of action. We recently identified 5-(,-hexamethylene)amiloride (HMA), an inhibitor of human Na/H exchanger isoform 1, as a promising scaffold for antifungal drug development. In this work, we carried out susceptibility testing of 45 6-substituted HMA and amiloride analogs against a panel of pathogenic fungi. A series of 6-(2-benzofuran)amiloride and HMA analogs that showed up to a 16-fold increase in activity against were identified. Hits from these series showed broad-spectrum activity against both basidiomycete and ascomycete fungal pathogens, including multidrug-resistant clinical isolates.

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