Predictive models, based on classification algorithms, for compounds potentially active as mitochondrial ATP-sensitive potassium channel openers
| Autor: | Lara Testai, Vincenzo Calderone, Maria Digiacomo, Anna Maria Paola Bianucci, Aldo Balsamo, Alessio Coi, Simona Rapposelli |
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| Rok vydání: | 2009 |
| Předmět: |
Quantitative structure–activity relationship
Cardiotonic Agents ATP-sensitive potassium channel Stereochemistry Clinical Biochemistry Quantitative Structure-Activity Relationship Pharmaceutical Science Biochemistry Set (abstract data type) KATP Channels Molecular descriptor Drug Discovery Benzopyrans Spiro Compounds Cardioprotective Agent Molecular Biology Molecular Structure Chemistry Organic Chemistry Support vector machine Statistical classification Models Chemical Test set Molecular Medicine Biological system Algorithms |
| Zdroj: | Bioorganic & Medicinal Chemistry. 17:5565-5571 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2009.06.028 |
| Popis: | Heart mitochondrial ATP-sensitive potassium channel (mito-K ATP channels) are deeply implicated in the self-defense mechanism of ischemic preconditioning. Therefore, exogenous molecules activating these channels are considered as a promising pharmacological tool to reduce the myocardial injury deriving from ischemia/reperfusion events. In our laboratory, a series of 4-spiro-substituted benzopyran derivatives were earlier synthesized and some of them exhibited anti-ischemic properties. In this study, the above compounds are exploited in order to develop QSAR models, based on classification approaches, capable of discriminating between the ones acting as cardioprotective agents and those that are unable to elicit such a property. Molecules belonging to the whole dataset were subjected to CODESSA and E-Dragon calculations in order to compute a large number of molecular descriptors enabling the construction of classification models. Based on the two program packages used, two different experiments were carried out, with the aim of identify batteries of models to be exploited for designing new cardioprotective agents from libraries of new chemical entities. Both model batteries satisfy the rigorous criteria adopted for the validation, either when tested on the training and test set, according to the most straightforward protocol, and when tested on an additional prediction set. They were proven to ensure successful applications in the field of cardioprotective agent design. |
| Databáze: | OpenAIRE |
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