Synthesis of an antifungal 1,2,4-triazole drug and establishment of a drug delivery system based on zeolitic imidazolate frameworks
Invasive fungal infections (IFIs) is a deadly fungal infection with a high mortality rate, particularly in patients having undergone prolonged use of chemotherapy drugs, transplant surgery and so on. Among them, Candida albicans has attracted great attention as an important pathogen. Triazoles such as Voriconazole and Fluconazole are considered to be one of the most effective and widely used antifungal drugs. However, the resistance of fungal to these drugs and the toxicity of triazoles to human normal cells are the main reasons for difficult treatment of invasive fungal infections. In this paper, a novel Trifluoromethyl -containing triazole compound TPHMB was designed and synthesized for the first time. The single crystal was obtained by solution evaporation method, and its molecular structure was determined by single crystal diffractometer. The activity against Candida albicans was detected (MIC90=8μg/ml). In addition, we have used metal organic framework ZIF-8 to establish an effective, less side effects via reducing non-specific aggregation in normal tissues and improving water solubility, low-toxicity and pH-responsive antifungal drug delivery system for the first time. Detailed material characterization confirmed the successful encapsulation of TPHMB in the ZIF-8 matrix and demonstrated good drug release at pH = 5, using plate count to find excellent synergy of ZIF-8 against Candida albicans. This study not only provides a reference for the development of new triazole drugs, but also develops the effective delivery of such drugs in vivo to achieve effective treatment of fungal infections.