Статья

3D-MEDNEs: An Alternative “In Silico” Technique for Chemical Research in Toxicology. 1. Prediction of Chemically Induced Agranulocytosis

Humberto González‐DíazUniversidad Central "Marta Abreu" de las Villas (UCLV)Yovani Marrero‐PonceChemical Bio-actives Center, Central University of “Las Villas” 54830, Cuba, Department of Pharmacy, Central University of “Las Villas” 54830, Cuba, and Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela 15782, SpainIvan HernándezChemical Bio-actives Center, Central University of “Las Villas” 54830, Cuba, Department of Pharmacy, Central University of “Las Villas” 54830, Cuba, and Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela 15782, SpainIyusmila BastidaChemical Bio-actives Center, Central University of “Las Villas” 54830, Cuba, Department of Pharmacy, Central University of “Las Villas” 54830, Cuba, and Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela 15782, SpainEsvieta TenorioChemical Bio-actives Center, Central University of “Las Villas” 54830, Cuba, Department of Pharmacy, Central University of “Las Villas” 54830, Cuba, and Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela 15782, SpainOslay NascoChemical Bio-actives Center, Central University of “Las Villas” 54830, Cuba, Department of Pharmacy, Central University of “Las Villas” 54830, Cuba, and Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela 15782, SpainEugenio UriarteChemical Bio-actives Center, Central University of “Las Villas” 54830, Cuba, Department of Pharmacy, Central University of “Las Villas” 54830, Cuba, and Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela 15782, SpainNilo CastañedoChemical Bio-actives Center, Central University of “Las Villas” 54830, Cuba, Department of Pharmacy, Central University of “Las Villas” 54830, Cuba, and Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela 15782, SpainMiguel Ángel Cabrera‐PérezChemical Bio-actives Center, Central University of “Las Villas” 54830, Cuba, Department of Pharmacy, Central University of “Las Villas” 54830, Cuba, and Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela 15782, SpainEdisleidy AguilaChemical Bio-actives Center, Central University of “Las Villas” 54830, Cuba, Department of Pharmacy, Central University of “Las Villas” 54830, Cuba, and Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela 15782, SpainOsmani MarreroChemical Bio-actives Center, Central University of “Las Villas” 54830, Cuba, Department of Pharmacy, Central University of “Las Villas” 54830, Cuba, and Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela 15782, SpainArmando MoralesChemical Bio-actives Center, Central University of “Las Villas” 54830, Cuba, Department of Pharmacy, Central University of “Las Villas” 54830, Cuba, and Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela 15782, SpainM. C. Sela PerezChemical Bio-actives Center, Central University of “Las Villas” 54830, Cuba, Department of Pharmacy, Central University of “Las Villas” 54830, Cuba, and Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela 15782, Spain

2003en

ABI

Аннотация

A novel approach to molecular negentropy from the point of view of Markov models is introduced. Stochastic negentropies (MEDNEs) are used to develop a linear discriminant analysis. The discriminant analysis produced a set of two discriminant functions, which gave rise to a very good separation of 93.38% of 151 chemicals (training series) into two groups. The total predictability (86.67%, i.e., 52 compounds out of 60) was tested by means of an external validation set. Randić's orthogonalization procedures allowed interpretation of the model while avoiding collinearity descriptors. On the other hand, factor analysis was used to suggest the relation of MEDNEs with other molecular descriptors and properties into a property space. Three principal factors (related to three orthogonal MEDNEs) can be used to explain approximately 90% of the variance of different molecular parameters of halobenzenes including bulk, energetic, dipolar, molecular surface-related, and hydrophobic parameters. Finally, preliminary experimental results coincide with a theoretical prediction when agranulocytosis induction by G-1, a novel microcidal that presents Z/E isomerism, is not detected.

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Идентификаторы

DOI: 10.1021/tx0256432

Цитирования и источники

Цитирований: 3Использованных источников: 0

Показатели — AkademScholar