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Pyrimidinetrione‐imidazoles as a Unique Structural Type of Potential Agents towards Candida Albicans : Design, Synthesis and Biological Evaluation
Author(s) -
Sui YanFei,
Ansari Mohammad Fawad,
Zhou ChengHe
Publication year - 2021
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.202100146
Subject(s) - corpus albicans , candida albicans , hela , fluconazole , cytotoxicity , triazole , chemistry , dna , imidazole , hek 293 cells , microbiology and biotechnology , antimicrobial , biology , antifungal , biochemistry , in vitro , gene , organic chemistry
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.