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Nghiên cứu in silico nhằm xác định các phân tử dựa trên thiadiazol mới tiềm năng làm ứng viên chống Covid-19 qua sàng lọc ảo phân cấp và mô phỏng động lực học phân tử
Tóm tắt
Trong nghiên cứu này, một loại mới của 1,3,4-thiadiazoles đã được phát triển bằng cách cho methyl 2-(4-hydroxy-3-methoxybenzylidene) hydrazine-1-carbodithioate phản ứng với các halide hydrazonoyl thích hợp với sự hiện diện của một vài giọt diisopropyl ethyl amine. Cấu trúc hóa học của các dẫn xuất mới tổng hợp được suy luận dựa trên dữ liệu vi phân tích và phổ. Sử dụng các kỹ thuật kết hợp giữa docking phân tử và mô phỏng động lực học phân tử, độ ổn định và các đặc tính liên kết của các hợp chất tổng hợp được đánh giá đối với bốn enzyme mục tiêu của SARS-CoV-2, bao gồm, protease chính (Mpro), protease giống papain (PLpro), RNA-polymerase phụ thuộc RNA (RdRp), và miền gắn kết thụ thể (RBD) của protein đột biến. Hợp chất 7 thể hiện độ ổn định gắn kết đầy hứa hẹn với các enzyme mục tiêu Mpro, PLpro, RdRp và RBD với điểm docking lần lượt là −11.4, −9.4, −8.2, và −6.8 kcal/mol. Ngoài ra, hợp chất 7 cũng thể hiện điểm docking MD MM-GBSA//100 ns là −35.9 kcal/mol đối với Mpro. Phân tích cấu trúc và năng lượng cho thấy sự ổn định của phức hợp 7-Mpro trong suốt 100 ns mô phỏng MD. Hơn nữa, hợp chất 7 tuân theo quy tắc năm của Lipinski, vì nó có khả năng hấp thụ, phân phối và sinh khả dụng đường uống chấp nhận được trong cơ thể. Do đó, hợp chất 7 được coi là một điểm khởi đầu hứa hẹn cho việc thiết kế các tác nhân điều trị tiềm năng chống lại Covid-19.
Từ khóa
#thiadiazole #Covid-19 #mô phỏng động lực học phân tử #docking phân tử #enzyme SARS-CoV-2Tài liệu tham khảo
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