Name
Title | ||
|---|---|---|
Predicting targets of compounds against neurological diseases using cheminformatic methodology. |
Abstract | ||
|---|---|---|
Recently developed multi-targeted ligands are novel drug candidates able to interact with monoamine oxidase A and B; acetylcholinesterase and butyrylcholinesterase; or with histamine N-methyltransferase and histamine H3-receptor (H3R). These proteins are drug targets in the treatment of depression, Alzheimer's disease, obsessive disorders, and Parkinson's disease. A probabilistic method, the Parzen-Rosenblatt window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Molecular structures were represented based on the circular fingerprint methodology. The same approach was used to build a "predictor" model from the DrugBank dataset to determine the main pharmacological groups of the compound. The study of off-target interactions is now recognised as crucial to the understanding of both drug action and toxicology. Primary pharmaceutical targets and off-targets for the novel multi-target ligands were examined by use of the developed cheminformatic method. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. The cheminformatic targets identifications were in agreement with four 3D-QSAR (H3R/D1R/D2R/5-HT2aR) models and by in vitro assays for serotonin 5-HT1a and 5-HT2a receptor binding of the most promising ligand (71/MBA-VEG8). |
Year | DOI | Venue |
|---|---|---|
2015 | 10.1007/s10822-014-9816-1 | Journal of computer-aided molecular design |
Keywords | Field | DocType |
Multi-targeted ligands,Circular fingerprints,Off-target study,ChE,MAO,Histamine H3 receptor,HMT | Histamine N-methyltransferase,Quantitative structure–activity relationship,chEMBL,Drug discovery,Drug action,In vitro toxicology,Pharmacology,Chemistry,Drug,DrugBank | Journal |
Volume | Issue | ISSN |
29 | 2 | 0920-654X |
Citations | PageRank | References |
0 | 0.34 | 10 |
Authors | ||
11 | ||
Name | Order | Citations | PageRank |
|---|---|---|---|
| Katarina Nikolic | 1 | 0 | 0.34 |
| Lazaros Mavridis | 2 | 103 | 7.47 |
| Oscar M Bautista-Aguilera | 3 | 0 | 0.34 |
| José Marco-Contelles | 4 | 0 | 0.34 |
| Holger Stark | 5 | 17 | 1.62 |
| Maria do Carmo Carreiras | 6 | 0 | 0.34 |
| Ilaria Rossi | 7 | 0 | 0.34 |
| Paola Massarelli | 8 | 0 | 0.34 |
| Danica Agbaba | 9 | 0 | 0.34 |
| Rona R Ramsay | 10 | 0 | 1.01 |
| John B O Mitchell | 11 | 384 | 32.48 |