2023
DOI: 10.1021/acs.jmedchem.3c00488
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Discovery of Pyrazolone Carbothioamide Derivatives as Inhibitors of the Pdr1-KIX Interaction for Combinational Treatment of Azole-Resistant Candidiasis

Abstract: Candida glabrata has emerged as an important opportunistic pathogen of invasive candidiasis due to increasing drug resistance. Targeting Pdr1-KIX interactions with small molecules represents a potential strategy for treating drug-resistant candidiasis. However, effective Pdr1-KIX inhibitors are rather limited, hindering the validation of target druggability. Here, new Pdr1-KIX inhibitors were designed and assayed. Particularly, compound B8 possessed a new chemical scaffold and exhibited potent KIX binding affi… Show more

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Cited by 3 publications
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“…Prior research has demonstrated the antibacterial and anti-inflammatory effects of pyrazoles [65], imidazoles [66], indazoles [67], isoindoles, and indolecarboxylic acids and derivatives [68,69]. These substances possess the ability to exert an impact on the intricate dynamics between lactic acid bacteria and their microbial counterparts, facilitating their sustenance and proliferation within a specific milieu through the suppression of growth and metabolic processes of the latter [70]. Furthermore, the presence of these compounds exhibits antioxidant effects; for instance, certain components of indolecarboxylic acids and derivatives may possess antioxidant activity that aids lactic acid bacteria in combating cellular oxidative stress [68].…”
Section: Metabolite Analysis Of L Plantarum A50mentioning
confidence: 99%
“…Prior research has demonstrated the antibacterial and anti-inflammatory effects of pyrazoles [65], imidazoles [66], indazoles [67], isoindoles, and indolecarboxylic acids and derivatives [68,69]. These substances possess the ability to exert an impact on the intricate dynamics between lactic acid bacteria and their microbial counterparts, facilitating their sustenance and proliferation within a specific milieu through the suppression of growth and metabolic processes of the latter [70]. Furthermore, the presence of these compounds exhibits antioxidant effects; for instance, certain components of indolecarboxylic acids and derivatives may possess antioxidant activity that aids lactic acid bacteria in combating cellular oxidative stress [68].…”
Section: Metabolite Analysis Of L Plantarum A50mentioning
confidence: 99%