Mô phỏng thiết kế các dẫn xuất chalcone-sulfonamide nhắm mục tiêu ức chế các enzyme histone deacetylase nhóm I
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Abstract
Histone deacetylase (HDAC) is a significant target in cancer therapy. In this work, the dataset of 32 metal-chelating compounds was designed based on the chalcone-sulfonamide scaffold. Molecular docking was conducted on HDAC class I family members. The results revealed robust interactions of these compounds with key amino acids at the active site, all displaying binding energies lower than -15 kJ/mol. Notably, derivative 20, a 2'-hydroxychalcone-sulfonamide compound bearing a meta-NO2 substituent, exhibited the most promising efficacy across all selected HDAC enzymes. This compound holds great potential for synthetic and biological evaluations in the future.
Tóm tắt
HDAC là mục tiêu quan trọng trong liệu pháp điều trị ung thư. Trong nghiên cứu này, bộ dữ liệu bao gồm 32 hợp chất có khả năng chelate với kim loại đã được thiết kế dựa trên khung sườn chalcone-sulfonamide. Docking phân tử đã được thực hiện trên các loại HDAC nhóm I. Kết quả cho thấy các hợp chất đều thể hiện các tương tác mạnh mẽ với các amino acid tại vị trí hoạt động. Năng lượng liên kết đều thấp hơn -15 kJ/mol. Đặc biệt, dẫn xuất 20 là hợp chất 2‘-hydroxychalcone-sulfonamide với nhóm thế meta-NO2 cho hiệu quả tốt nhất với cả ba enzyme HDAC. Đây được xem là ứng viên tiềm năng cho các nghiên cứu tổng hợp và đánh giá hoạt tính sinh học trong tương lai.
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