ArticleACS chemical neuroscience2013
Model for high-throughput screening of multitarget drugs in chemical neurosciences: synthesis, assay, and theoretic study of rasagiline carbamates.
Article in ACS chemical neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 53 citations in OpenAlex.
- On the additive artificial intelligence-based discovery of nanoparticle neurodegenerative disease drug delivery systems.Beilstein journal of nanotechnology · 2024Article
- PTML modeling for peptide discovery: in silico design of non-hemolytic peptides with antihypertensive activity.Molecular diversity · 2022Article
- Neuroprotective Function of Rasagiline and Selegiline, Inhibitors of Type B Monoamine Oxidase, and Role of Monoamine Oxidases in Synucleinopathies.International journal of molecular sciences · 2022Review
- QSAR Modeling for Multi-Target Drug Discovery: Designing Simultaneous Inhibitors of Proteins in Diverse Pathogenic Parasites.Frontiers in chemistry · 2021Article
- Perturbation-Theory Machine Learning (PTML) Multilabel Model of the ChEMBL Dataset of Preclinical Assays for Antisarcoma Compounds.ACS omega · 2020Article
- Multi-Target Chemometric Modelling, Fragment Analysis and Virtual Screening with ERK Inhibitors as Potential Anticancer Agents.Molecules (Basel, Switzerland) · 2019Article
- Development of Multi-Target Chemometric Models for the Inhibition of Class I PI3K Enzyme Isoforms: A Case Study Using QSAR-Co Tool.International journal of molecular sciences · 2019Article
- Article
- Computer-Aided Drug Design Applied to Marine Drug Discovery: Meridianins as Alzheimer's Disease Therapeutic Agents.Marine drugs · 2017Article
- Multi-output model with Box-Jenkins operators of linear indices to predict multi-target inhibitors of ubiquitin-proteasome pathway.Molecular diversity · 2015Article
- Prediction of multi-target networks of neuroprotective compounds with entropy indices and synthesis, assay, and theoretical study of new asymmetric 1,2-rasagiline carbamates.International journal of molecular sciences · 2014Article
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The disappointing results obtained in recent clinical trials renew the interest in experimental/computational techniques for the discovery of neuroprotective drugs. In this context, multitarget or multiplexing QSAR models (mt-QSAR/mx-QSAR) may help to predict neurotoxicity/neuroprotective effects of drugs in multiple assays, on drug targets, and in model organisms. In this work, we study a data set downloaded from CHEMBL; each data point (>8000) contains the values of one out of 37 possible measures of activity, 493 assays, 169 molecular or cellular targets, and 11 different organisms (including human) for a given compound. In this work, we introduce the first mx-QSAR model for neurotoxicity/neuroprotective effects of drugs based on the MARCH-INSIDE (MI) method. First, we used MI to calculate the stochastic spectral moments (structural descriptors) of all compounds. Next, we found a model that classified correctly 2955 out of 3548 total cases in the training and validation series with Accuracy, Sensitivity, and Specificity values>80%. The model also showed excellent results in Computational-Chemistry simulations of High-Throughput Screening (CCHTS) experiments, with accuracy=90.6% for 4671 positive cases. Next, we reported the synthesis, characterization, and experimental assays of new rasagiline derivatives. We carried out three different experimental tests: assay (1) in the absence of neurotoxic agents, assay (2) in the presence of glutamate, and assay (3) in the presence of H2O2. Compounds 11 with 27.4%, 8 with 11.6%, and 9 with 15.4% showed the highest neuroprotective effects in assays (1), (2), and (3), respectively. After that, we used the mx-QSAR model to carry out a CCHTS of the new compounds in >400 unique pharmacological tests not carried out experimentally. Consequently, this model may become a promising auxiliary tool for the discovery of new drugs for the treatment of neurodegenerative diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.