Anti-Inflammatory Potential of 1-Aryl-6,7-Dimethoxy-1,2,3,4-Tetrahydroisoquinolines: Structure–Activity Relationship and COX-2 Binding
Annotatsiya
Non-steroidal anti-inflammatory drugs (NSAIDs) are used globally for their pain-relieving and fever-reducing properties. However, excessive intake of NSAIDs can have harmful effects on multiple body systems, including the cardiovascular, gastrointestinal, hepatic, renal, and nervous systems. The anti-inflammatory activity of 34 derivatives of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline was investigated in vivo. A relationship between the activity of the compounds and the nature of their substituents, as well as their positional and mutual arrangement in the C ring (1-Ar-), was established. In silico modeling of these 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives’ interaction with the COX-2 (PDB ID: 1PXX) active site revealed that the nitro-derivatives exhibited the highest stability owing to their superior capacity for electrostatic and hydrogen bond formation compared to brominated compounds. These data on the effects of the substituents –NH2, –OH, and –OCH3 in ring C (1-Ar-) of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines on anti-inflammatory activity promote the search for new, highly effective derivatives within this series.