biostudies-literatureUnknown12Afifi HIn this study, we report the design and synthesis of a new series of pyrrolopyrimidine derivatives developed as dual-target nonsteroidal anti-inflammatory agents (NSAIDs). The compounds were evaluated for anti-inflammatory properties, cyclooxygenase-1/2 (COX-1/COX-2) inhibitory activity, and angiotensin-converting enzyme 2 (ACE2)-blocking activity in lipopolysaccharide (lipopolysaccharide)-stimulated RAW264.7 cells. Among the synthesized molecules, compounds <b>5a</b> and <b>5b</b> showed potent dual inhibitory activity, which was supported by molecular docking and molecular dynamics simulations. These findings highlight the potential of selective COX-2 inhibitors with concurrent ACE2 blockade as a promising therapeutic approach for controlling inflammation and modulating pathways relevantFrontiers in molecular biosciences1710650https://www.ebi.ac.uk/biostudies/studies/S-EPMC12815825biostudies-literaturePyrrolopyrimidine derivatives as dual COX-2/ACE2 inhibitors: design, synthesis, and anti-inflammatory evaluation.PMC12815825Taha HGharib AFAfifi HEl-Haggar RFatahala SSMahgoub SAly OSayed AIAbd El-Hameed RHfalsePyrrolopyrimidine derivatives as dual COX-2/ACE2 inhibitors: design, synthesis, and anti-inflammatory evaluation.In this study, we report the design and synthesis of a new series of pyrrolopyrimidine derivatives developed as dual-target nonsteroidal anti-inflammatory agents (NSAIDs). The compounds were evaluated for anti-inflammatory properties, cyclooxygenase-1/2 (COX-1/COX-2) inhibitory activity, and angiotensin-converting enzyme 2 (ACE2)-blocking activity in lipopolysaccharide (lipopolysaccharide)-stimulated RAW264.7 cells. Among the synthesized molecules, compounds <b>5a</b> and <b>5b</b> showed potent dual inhibitory activity, which was supported by molecular docking and molecular dynamics simulations. These findings highlight the potential of selective COX-2 inhibitors with concurrent ACE2 blockade as a promising therapeutic approach for controlling inflammation and modulating pathways relevant2025-01-01T00:00:00Z20252026-06-06T17:47:53.637Z2026-06-03T03:10:44.993ZS-EPMC128158254156786210.3389/fmolb.2025.1710650