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Xác thực thực nghiệm và nghiên cứu docking của các dẫn xuất flavone trên aldose reductase liên quan đến bệnh võng mạc tiểu đường, bệnh thần kinh và bệnh thận
Tóm tắt
Enzyme aldoreductase, đóng vai trò quan trọng trong quá trình sinh bệnh của bệnh võng mạc tiểu đường, bệnh thần kinh và bệnh thận, đã được tinh chế từ thấu kính trâu bò, và hoạt tính ức chế của nó đã được nghiên cứu với các dẫn xuất flavone tổng hợp 1-(2-hydroxyphenyl)ethanone làm vật liệu khởi đầu. Nghiên cứu thực nghiệm cho thấy 2-chloroflavone có hoạt tính ức chế ít hơn từ 60-70% so với các flavone khác được sử dụng trong nghiên cứu. Để xác nhận kết quả thực nghiệm bằng phương pháp tính toán, các nghiên cứu docking của các dẫn xuất flavone mới tổng hợp đã được thực hiện với enzyme aldose reductase, và các kết quả chỉ ra rằng 3-iodo, 4-methyl, 5-chloroflavone và 2-chloroflavone gắn kết với độ affinities cao và thấp hơn. Các nghiên cứu docking với site directed mutagenesis của các vị trí Val47Ile, Tyr48His, Pro121Phe, Trp219Tyr, Cys298Ala, Leu300Pro, Ser302Arg, và Cys303Asp của enzyme đã làm thay đổi hoạt tính ức chế của aldose reductase. Giá trị hồi quy (R²) là 0.81 giữa các điểm số docking của các chất ức chế đã biết và logIC50 thực nghiệm cho thấy độ tin cậy của các nghiên cứu docking. Hoạt tính sinh học và tính chất gây ung thư dự đoán rằng 3-iodo, 4-methyl, 5-chloroflavone là chất ức chế flavone tốt nhất đối với aldose reductase.
Từ khóa
Tài liệu tham khảo
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