Chiến lược nhắm mục tiêu vào DNA dựa trên cấu trúc các dẫn xuất chalcone mang dị vòng như là tác nhân chống ung thư tiềm năng
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Abstract
Chalcone scaffolds play an important role in anticancer drug design. In this article, the chalcone derivatives containing heterocyclic moiety (quinazolinone, benzimidazole, benzoxazole and 1,3,4-oxadiazole) with potential anticancer activity have been reviewed on the prediction of DNA-binding. Compounds provided excellent results for DNA intercalation, compared with those of the standard at a molecular level. Molecular dynamics simulations were performed for the top four docked complexes, which indicated the structural stability of the DNA–ligand complexes. ADMET prediction was also performed for the top ligands. In summary, this study encouraged the synthesis of designed compounds and the study of their in vitro DNA interactive ability and cytotoxicity. This class of compounds might be helpful for the development of new and potential multi-target anticancer agents or drugs in the future.
Tóm tắt
Khung sườn chalcone đóng vai trò quan trọng trong công cuộc thiết kế các loại thuốc chống ung thư. Trong nghiên cứu này, các dẫn xuất chalcone chứa hợp chất dị vòng là quinazolinone, benzimidazole, benzoxazole và 1,3,4-oxadiazole với hoạt tính chống ung thư tiềm năng đã được xem xét về khả năng gắn kết với DNA. Các hợp chất cho kết quả xen kẽ vào DNA chặt so với hợp chất đối chứng trên phương diện cấp độ phân tử. Mô phỏng động lực học đã được thực hiện cho bốn phức hợp tốt nhất, kết quả cho thấy sự ổn định về cấu trúc đã được gắn kết ở các phức hợp phối tử-DNA. Dự đoán về ADMET cũng đã được thực hiện cho các phối tử này. Tóm lại, nghiên cứu này khuyến khích tổng hợp các hợp chất chalcone chứa dị vòng, nghiên cứu khả năng tương tác với DNA và hiệu quả gây độc tế bào của chúng bằng các mô hình thực nghiệm in vitro. Nhóm hợp chất này có thể hữu ích cho việc phát triển các tác nhân hoặc thuốc chống ung thư đa mục tiêu mới và tiềm năng trong tương lai.
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