title: Brain-inspired cheminformatics of drug-target brain interactome, synthesis, and assay of TVP1022 derivatives.
abstract: The use of Cheminformatics tools is gaining importance in the field of translational research from Medicinal Chemistry to Neuropharmacology. In particular, we need it for the analysis of chemical information on large datasets of bioactive compounds. These compounds form large multi-target complex networks (drug-target interactome network) resulting in a very challenging data analysis problem. Artificial Neural Network (ANN) algorithms may help us predict the interactions of drugs and targets in CNS interactome. In this work, we trained different ANN models able to predict a large number of drug-target interactions. These models predict a dataset of thousands of interactions of central nervous system (CNS) drugs characterized by > 30 different experimental measures in >400 different experimental protocols for >150 molecular and cellular targets present in 11 different organisms (including human). The model was able to classify cases of non-interacting vs. interacting drug-target pairs with satisfactory performance. A second aim focus on two main directions: the synthesis and assay of new derivatives of TVP1022 (S-analogues of rasagiline) and the comparison with other rasagiline derivatives recently reported. Finally, we used the best of our models to predict drug-target interactions for the best new synthesized compound against a large number of CNS protein targets.
authors.affiliation: Department of Organic Chemistry, USC, 15782 Santiago de Compostela, Spain; IMQ Zorrotzaurre Clinic, 48014 Bilbao, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Romero-Durán
authors.affiliation: Department of Organic Chemistry, USC, 15782 Santiago de Compostela, Spain.
authors.forename: Nerea
authors.initials: N
authors.lastname: Alonso
authors.affiliation: Department of Pharmacology, USC, 15782 Santiago de Compostela, Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Yañez
authors.affiliation: Department of Organic Chemistry, USC, 15782 Santiago de Compostela, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Caamaño
authors.affiliation: Department of Organic Chemistry, USC, 15782 Santiago de Compostela, Spain. Electronic address: xerardo.garcia@usc.es.
authors.forename: Xerardo
authors.initials: X
authors.lastname: García-Mera
authors.affiliation: Department of Organic Chemistry II, University of Basque Country UPV/EHU, 48940 Leioa, Spain; Ikerbasque, Basque Foundation for Science, 48011 Bilbao, Spain. Electronic address: humberto.gonzalezdiaz@ehu.eus.
authors.forename: Humberto
authors.initials: H
authors.lastname: González-Díaz
mesh_terms: D000465:Algorithms; D000818:Animals; D001921:Brain / Q000187:drug effects*; D019295:Computational Biology; D016503:Drug Delivery Systems; D006801:Humans; D007189:Indans / Q000493:pharmacokinetics / Q000494:pharmacology*; D016571:Neural Networks, Computer; D018696:Neuroprotective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D012372:ROC Curve
chemical_list: D007189:Indans; D018696:Neuroprotective Agents; C031967:rasagiline
keywords: Alzheimer disease; Amitriptyline (PubChem CID: 11065); Apomorphine (PubChem CID: 6005); Artificial neural networks; Asymmetric synthesis; CNS drug-target interactome; CNS drugs; ChEMBL; Chemoinformatics; Fluoxetine (PubChem CID: 3386); Gamma-amino butyric acid PubChem CID: 119); Metoclopramide (PubChem CID: 4168); Neuroprotective effects; Nicotine (PubChem CID: 942); Olanzapine (PubChem CID: 4585); Phenytoin (PubChem CID: 1775); Rasagiline (PubChem CID: 3052776); Rasagiline analogues; Resveratrol (PubChem CID: 445154)