Search for: [Abstract = "gest a cumulative, more potent therapeutic effect. The additional anti\-remodeling effect achieved by inhibiting PDE8A allows for broadening the spectrum of action of the proposed multifunctional ligands, giving an opportunity for an effective and multi\-level therapeutic approach. This doctoral dissertation aimed to propose and validate a strategy using computer molecular modeling techniques in the search for multi\-target\-directed ligands that block phosphodiesterases 4B, 8A, and the TRPA1 ion channel, and to select novel chemotypes for MTDLs. The research was conducted in two ways using the approach based on the structures of biological targets and based on the structures of ligands. For the structure\-based approach, structural models were appropriately prepared for each of the biological targets that demonstrated the binding mode of the reference inhibitors and antagonists in individual active pockets. For the TRPA1 ion channel, a new binding pocket was predicted and a potential binding mode for its antagonist was proposed. Due to the presence of two binding sites where TRPA1 antagonists could interact, two models based on experimental structures of the ion channel, deposited in the PDB \(Protein Data Bank\) database, were also used in the study. In the case of PDE8A, a possible binding mode of its most active inhibitor was presented, which was proposed based on available lit"]
