Agrochemical Lessons for Infectious Disease Research: New Resistance Breaking Antifungal Hits against Candida auris

ACS Medicinal Chemistry Letters
2023.0

Abstract

Analysis of the history of the invention of the block-buster antifungal drug Fluconazole underscores the importance of agrochemical research on drug discovery and development. The multidrug resistant fungal pathogen <i>Candida auris</i> is now responsible for serious morbidity and mortality among immuno-compromised and long-term resident hospital patients globally. New drugs against <i>C. auris</i> are urgently needed. A focused screening of 1487 fungicides from the BASF agrochemical collection gave several potent inhibitors of <i>C. auris</i> with yet noncommercialized modes of action. The hits showed only minor activity loss against the azole-resistant <i>C. auris</i> strain CDC 0385 and low to moderate cytotoxicity to human HepG2 cells. Aminopyrimidine <b>4</b> showed high activity against resistant strains and selectivity in a HepG2 cells assay and is a potential hit candidate for further optimization.

Knowledge Graph

Similar Paper

Agrochemical Lessons for Infectious Disease Research: New Resistance Breaking Antifungal Hits against Candida auris
ACS Medicinal Chemistry Letters 2023.0
Antifungal activity of substituted aurones
Bioorganic &amp; Medicinal Chemistry Letters 2017.0
Benzofuro[3,2-d]pyrimidines inspired from cercosporamide CaPkc1 inhibitor: Synthesis and evaluation of fluconazole susceptibility restoration
Bioorganic &amp; Medicinal Chemistry Letters 2018.0
Modulation of key antioxidant enzymes and cell cycle arrest as a possible antifungal mode of action of cinnamaldehyde based azole derivative
Bioorganic &amp; Medicinal Chemistry Letters 2022.0
Novel 2-Aryloxazoline Compounds Exhibit an Inhibitory Effect on Candida spp., Including Antifungal-Resistant Isolates
ACS Medicinal Chemistry Letters 2020.0
Generation of Broad-Spectrum Antifungal Drug Candidates from the Natural Product Compound Aureobasidin A
ACS Medicinal Chemistry Letters 2015.0
High-Throughput-Screening-Based Identification and Structure–Activity Relationship Characterization Defined (S)-2-(1-Aminoisobutyl)-1-(3-chlorobenzyl)benzimidazole as a Highly Antimycotic Agent Nontoxic to Cell Lines
Journal of Medicinal Chemistry 2011.0
Optimization and Evaluation of Novel Antifungal Agents for the Treatment of Fungal Infection
Journal of Medicinal Chemistry 2021.0
Novel Macrocyclic Amidinoureas: Potent Non-Azole Antifungals Active against Wild-Type and Resistant Candida Species
ACS Medicinal Chemistry Letters 2013.0
Drug repurposing strategy II: from approved drugs to agri-fungicide leads
The Journal of Antibiotics 2023.0