Khảo sát các dẫn xuất azo-thiohydantoins mới tổng hợp như là các chất ức chế phosphatase kiềm tiềm năng thông qua đặc trưng sinh hóa tiên tiến và phương pháp mô hình phân tử

Springer Science and Business Media LLC - 2024
Hafiz Muhammad Attaullah1, Syeda Abida Ejaz1, Pervaiz Ali Channar2, Aamer Saeed3, Rabail Ujan4, Seema Zargar5, Sajid Ali Channar4, Reshma Sahito6, Tanveer A. Wani7, Qamar Abbas8,9
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
2Department of Basic Sciences and Humanities, Faculty of Information Science and Humanities, Dawood University of Engineering and Technology, Karachi, Pakistan
3Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan
4Dr. M. A. Kazi Institute of Chemistry, University of Sindh Jamshoro, Pakistan
5Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia
6Department of Zoology, University of Sindh, Jamshoro, Pakistan
7Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
8Department of Biology, College of Science, University of Bahrain, Sakhir, Kingdom of Bahrain
9College of Natural Sciences, Department of Biological Sciences, Kongju National University, Gongju, Republic of Korea

Tóm tắt

Trong nghiên cứu hiện tại, các dẫn xuất Azo-Thiohydantoins đã được tổng hợp và đặc trưng bởi việc sử dụng nhiều kỹ thuật quang phổ khác nhau bao gồm FTIR, 1H-NMR, 13C-NMR, phân tích nguyên tố và phân tích HRMS. Các hợp chất đã được đánh giá về hoạt tính phosphatase kiềm và quan sát thấy rằng trong số tất cả các hợp chất đã tổng hợp, dẫn xuất 7e thể hiện hoạt tính ức chế đáng kể (IC50 = 0.308 ± 0.065 µM), vượt qua chất ức chế tiêu chuẩn (L–Phenyl alanine, IC50 = 80.2 ± 1.1 µM). Cùng với đó, các dẫn xuất này đã được khảo sát một cách toàn diện về các tính chất điện tử và phản ứng của các hợp chất đã tổng hợp bằng cách sử dụng các phép tính Lý thuyết Hàm mật độ (DFT), nơi mà các kết quả được tìm thấy rất khả quan và các hợp chất tổng hợp được xác định là ổn định. Sau đó, các đánh giá SwissADME đã làm nổi bật các hợp chất có các đặc tính lý hóa thuận lợi, bao gồm khả năng hòa tan và tính tương tự thuốc. Mô phỏng docking phân tử đã thể hiện khả năng gắn kết mạnh mẽ của các dẫn xuất 7f và 7e với phosphatase kiềm ruột (IAP), thêm vào đó là sự hỗ trợ của các mô phỏng Động lực học Phân tử (MD). Sự tích hợp toàn diện giữa các phương pháp thực nghiệm và tính toán này làm sáng tỏ các ứng dụng điều trị tiềm năng của các hợp chất đã tổng hợp. Bằng việc cung cấp một cuộc điều tra chi tiết về các khía cạnh này, nghiên cứu này mở ra các hướng đi cho sự phát triển các hợp chất dược lý hoạt động mới với nhiều ứng dụng đa dạng.

Từ khóa

#azo-thiohydantoins #phosphatase kiềm #DFT #mô phỏng phân tử #hoạt tính ức chế

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