title: Prediction of multi-target networks of neuroprotective compounds with entropy indices and synthesis, assay, and theoretical study of new asymmetric 1,2-rasagiline carbamates.
abstract: In a multi-target complex network, the links (L(ij)) represent the interactions between the drug (d(i)) and the target (t(j)), characterized by different experimental measures (K(i), K(m), IC50, etc.) obtained in pharmacological assays under diverse boundary conditions (c(j)). In this work, we handle Shannon entropy measures for developing a model encompassing a multi-target network of neuroprotective/neurotoxic compounds reported in the CHEMBL database. The model predicts correctly >8300 experimental outcomes with Accuracy, Specificity, and Sensitivity above 80%-90% on training and external validation series. Indeed, the model can calculate different outcomes for >30 experimental measures in >400 different experimental protocolsin relation with >150 molecular and cellular targets on 11 different organisms (including human). Hereafter, we reported by the first time the synthesis, characterization, and experimental assays of a new series of chiral 1,2-rasagiline carbamate derivatives not reported in previous works. The experimental tests included: (1) assay in absence of neurotoxic agents; (2) in the presence of glutamate; and (3) in the presence of H2O2. Lastly, we used the new Assessing Links with Moving Averages (ALMA)-entropy model to predict possible outcomes for the new compounds in a high number of pharmacological tests not carried out experimentally.
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela (USC), Santiago de Compostela 15782, Spain. fcojavier.romero@rai.usc.es.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Romero Durán
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela (USC), Santiago de Compostela 15782, Spain. nerea.alonso@rai.usc.es.
authors.forename: Nerea
authors.initials: N
authors.lastname: Alonso
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela (USC), Santiago de Compostela 15782, Spain. molga.caamano@usc.es.
authors.forename: Olga
authors.initials: O
authors.lastname: Caamaño
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela (USC), Santiago de Compostela 15782, Spain. xerardo.garcía@usc.es.
authors.forename: Xerardo
authors.initials: X
authors.lastname: García-Mera
authors.affiliation: Department of Pharmacology, University of Santiago de Compostela (USC), Santiago de Compostela 15782, Spain. matilde.yanez@usc.es.
authors.forename: Matilde
authors.initials: M
authors.lastname: Yañez
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela (USC), Santiago de Compostela 15782, Spain. fprado@uqroo.mx.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Prado-Prado
authors.affiliation: Department of Organic Chemistry II, Faculty of Science and Technology, University of the Basque Country UPV/EHU, Leioa 48940, Spain. humberto.gonzálezdíaz@ehu.es.
authors.forename: Humberto
authors.initials: H
authors.lastname: González-Díaz
mesh_terms: D000465:Algorithms; D000818:Animals; D002219:Carbamates / Q000138:chemical synthesis / Q000494:pharmacology*; D002470:Cell Survival; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D062313:Databases, Pharmaceutical; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D019277:Entropy; D018698:Glutamic Acid / Q000494:pharmacology; D007189:Indans / Q000494:pharmacology*; D008956:Models, Chemical; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D051381:Rats
chemical_list: D002219:Carbamates; D007189:Indans; D018696:Neuroprotective Agents; C031967:rasagiline; D018698:Glutamic Acid