Conformation-Independent QSAR Study on Human Epidermal Growth Factor Receptor-2 (HER2) Inhibitors
| Autor: | Karolina Wróbel, Silvina E. Fioressi, Eduardo A. Castro, Pablo R. Duchowicz, Daniel E. Bacelo, N. E. Ibezim |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Quantitative structure–activity relationship 010304 chemical physics Stereochemistry Chemistry QSAR Física General Chemistry Computational biology Química 01 natural sciences 03 medical and health sciences 030104 developmental biology Molecular descriptor HER2 0103 physical sciences tyrosine kinase protein cancer Human Epidermal Growth Factor Receptor 2 Function (biology) Ciencias Exactas |
| Zdroj: | SEDICI (UNLP) Universidad Nacional de La Plata instacron:UNLP |
| Popis: | Inhibition of HER2 (human epidermal growth factor receptor 2) expression and function is required in several cancer treatments. Numerous compounds with very different molecular structures have been suggested as HER2 inhibitors. Here we perform quantitative structure-activity relationship (QSAR) analysis on 444 of such compounds to investigate the molecular properties that may influence its efficiency. Models based on 1D and 2D flexible molecular descriptors are proposed to develop simple models based solely on constitutional and topological molecular features. A large number of nonconformational descriptors (17974) was used to thoroughly explore the structural characteristics that influence the HER2 inhibitory activity. Three different approaches were explored using: 1) Molecular Descriptors, 2) Flexible Molecular Descriptors, and 3) Hybrid Descriptors. A QSAR model for HER2 inhibitors was successfully developed. Some properties such as electronegativity, aromatic character, and the presence of amino groups appear as molecular characteristics that may have influence in the HER2 inhibitory activity. Facultad de Ciencias Exactas Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas |
| Databáze: | OpenAIRE |
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