Design, Synthesis, and In Vitro and In Vivo Antifungal Activity of Novel Triazoles Containing Phenylethynyl Pyrazole Side Chains

Abstract

A series of triazole derivatives containing phenylethynyl pyrazole moiety as side chain were designed, synthesized, and most of them exhibited good in vitro antifungal activities. Especially, compounds 5k and 6c showed excellent in vitro activities against C. albicans (MIC = 0.125, 0.0625 μg/mL), C. neoformans (MIC = 0.125, 0.0625 μg/mL), and A. fumigatus (MIC = 8.0, 4.0 μg/mL). Compound 6c also exerted superior activity to compound 5k and fluconazole in inhibiting hyphae growth of C. albicans and inhibiting drug-resistant strains of C. albicans, and it could reduce fungal burdens in mice kidney at a dosage of 1.0 mg/kg. An in vivo efficacy evaluation indicated that 6c could effectively protect mice models from C. albicans infection at doses of 0.5, 1.0, and 2.0 mg/kg. These results suggested that compound 6c deserves further investigation.

Inhibition of apoptosis and biofilm formation in Candida auris by click-synthesized triazole-bridged quinoline derivatives

“…† 2.2 Antifungal activity 2.2.1 Antifungal activity of the derivatives QT1-QT10. Based on a previously published report, 27 the MIC values were categorized as excellent (MIC < 0.25 mg mL −1 ), good (MIC = 0.25-1.0 mg mL −1 ) and moderate (MIC = 1.0-64.0 mg mL −1 ). In this study, 10 newly synthesized compounds were tested against C. auris MRL6057.…”

Bio-Oriented Synthesis and Molecular Docking Studies of 1,2,4-Triazole Based Derivatives as Potential Anti-Cancer Agents against HepG2 Cell Line

“…Our ongoing research focuses on the design and synthesis of pharmacologically active, diverse polyvalent scaffolds as anti-cancer agents. The versatile nature of 1,2,4-triazole has been reported to be of great importance in medicinal chemistry, such as for its anti-cancer [ 20 ], anti-fungal [ 21 ], anti-bacterial [ 22 ], anti-microbial, and anti-tumor properties [ 23 ], as well as pyrophosphatases and phosphodiesterase [ 24 ]. Acetamide has been identified as the most significant pharmacophore of anti-cancer drugs [ 25 ].…”

Synthesis, Antifungal Activities, Molecular Docking and Molecular Dynamic Studies of Novel Quinoxaline-Triazole Compounds

“…As antifungal agents, azoles act through inhibition of fungal lanosterol 14-α-demethylases (CYP51), an enzyme required to catalyze the oxidative removal of 14-α-demethylases in sterol biosynthesis by fungi . Fluconazole is used in the treatment of fungal infections as a drug with high oral bioavailability and therapeutic index.…”

“…5 As antifungal agents, azoles act through inhibition of fungal lanosterol 14-α-demethylases (CYP51), an enzyme required to catalyze the oxidative removal of 14-α-demethylases in sterol biosynthesis by fungi. 6 Fluconazole is used in the treatment of fungal infections as a drug with high oral bioavailability and therapeutic index. To overcome some of the shortcomings when using these first generation agents, second generation analogues such as voriconazole, ketoconazole, albaconazole and posaconazole have been developed.…”