AILDE Computer-Aided Discovery of Novel Ibuprofen-Coumarin Antitumor Lead Compounds Targeting Cyclooxygenase-2.

ABSTRACT: Starting from three ibuprofen-coumarin hit compounds, we designed 18 derivative compounds targeting cyclooxygenase-2 (COX-2) by introducing different substituents onto them by using the computational auto in silico ligand directing evolution (AILDE) method. After synthesizing and testing the activity, we found that 6 representative compounds have micromolar enzyme inhibitory activity against COX-2. Additionally, 16 compounds have shown certain inhibitory activity in cervical cancer cells. Among these compounds, 6c (IC₅₀ = 0.606 μM, HeLa) and 7g (IC₅₀ = 0.783 μM, HeLa) have exhibited excellent activity, which is approximately 10 times better than the commercial drug gefitinib. According to molecular simulation results, the halogen atoms of 6c and <

SUBMITTER: Wu F 

PROVIDER: S-EPMC11447854 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature