Anti-Inflammatory Potential of 1-Aryl-6,7-Dimethoxy-1,2,3,4-Tetrahydroisoquinolines: Structure-Activity Relationship and COX-2 Binding.

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.