Theoretical and pharmacological study of multitarget compounds against neurological diseases

Multi-target ligands, recently developed in our laboratories, are novel drug candidates able to interact with MAO-A and B; AChE and BuChE; or with HMT and H3R, as essential drug targets in the treatment of Alzheimer's disease, depression, obsessive disorders, and Parkinson's disease. Using the refined ChEMBL families and our validated cheminformatic approach of the protein target prediction we have identified the pharmaceutical target and of-targets associated with the 134 multipotent compounds able to interact with MAO-A and B; AChE and BuChE; or with HMT and H3R. High affnities for the top ranked off-targets of the selected ligands were confirmed by in vitro testing (5-HT1aR, 5-HT2aR) and 3D-QSAR(H3R/D1R/D2R/5-HT2aR) studies. Multi-target ligands with possible additional beneficial pharmacological activities were selected for further study.