Evaluation of biological activity of some pyridine derivatives on perfusion pressure and their interaction with the M₂ muscarinic receptor

Abstract

The aim of this study was to evaluate the biological activity of some pyridine derivatives (compounds 1 to 15) on perfusion pressure in an isolated rat heart model. Furthermore, theoretical interaction of pyridine derivatives with the M2 muscarinic receptor was determined using acetylcholine, AF‐DX 116 and the 3uon protein as theoretical tools in a docking model. Results showed that pyridine derivatives 6, 9, and 13 decreased perfusion pressure compared to control conditions and compounds 1‐5, 7, 8, 10‐12, 14, and 15. Furthermore, theoretical data indicates that different amino acid residues are involved in the interaction of pyridine derivatives with the protein surface. Other data indicate that the inhibition constant was lower for compounds 6, 9 and 13 compared to acetylcholine and AF‐DX 116. In conclusion, all these data suggest that pyridine derivatives 6, 9 and 13 can produce changes in perfusion pressure possibly through activation of the M2 muscarinic receptor, and this phenomenon could depend on the different functional groups involved in its chemical structure.