Pyrimidinetrione‐imidazoles as a Unique Structural Type of Potential Agents towards Candida Albicans : Design, Synthesis and Biological Evaluation
| Autor: | Cheng-He Zhou, Mohammad Fawad Ansari, Yan-Fei Sui |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Antifungal Agents
Cell Survival Antifungal drug Microbial Sensitivity Tests 010402 general chemistry Hemolysis 01 natural sciences Biochemistry Cell Line HeLa Sterol 14-Demethylase Structure-Activity Relationship chemistry.chemical_compound Candida albicans medicine Humans Cytotoxicity Membrane potential Binding Sites biology 010405 organic chemistry Chemistry Organic Chemistry Imidazoles Drug Resistance Microbial General Chemistry biology.organism_classification Corpus albicans 0104 chemical sciences Molecular Docking Simulation Pyrimidines Drug Design Fluconazole DNA medicine.drug |
| Zdroj: | Chemistry – An Asian Journal. 16:1417-1429 |
| ISSN: | 1861-471X 1861-4728 |
| DOI: | 10.1002/asia.202100146 |
| Popis: | Substantial morbidity and mortality of fungal infections have aroused concerns all over the world, and common Candida spp. currently bring about severe systemic infections. A series of pyrimidinetrione-imidazole conjugates as potentially antifungal agents were developed. Bioassays manifested that 4-fluobenzyl pyrimidinetrione imidazole 5 f exerted favorable inhibition towards C. albicans (MIC=0.002 mM), being 6.5 folds more active than clinical antifungal drug fluconazole (MIC=0.013 mM). Preliminary mechanism research indicated that compound 5 f could not only depolarize membrane potential but also permeabilize the membrane of C. albicans. Molecular docking was operated to simulate the interaction mode between molecule 5 f and CYP51. In addition, hybrid 5 f might form 5 f-DNA supramolecular complex via intercalating into DNA. The interference of membrane and DNA might contribute to its fungicidal capacity with no obvious tendency to induce the resistance against C. albicans. Conjugate 5 f endowed good blood compatibility as well as low cytotoxicity towards HeLa and HEK-293T cells. |
| Databáze: | OpenAIRE |
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