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Quantitative Structure - Retention Relationship study of benzodiazepines using adaptive neuro fuzzy inference system as feature selection method

Jalali Heravi, M ; Sharif University of Technology | 2008

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  1. Type of Document: Article
  2. DOI: 10.1002/qsar.200630163
  3. Publisher: 2008
  4. Abstract:
  5. A Quantitative Structure-Retention Relationship (QSRR) study of 32 benzodiazepines is performed in this work. Two feature selection methods of Adaptive Neuro Fuzzy Inference System (ANFIS) and a stepwise regression approach adopted for the Multiple Linear Regressions (MLR) were used to predict the Liquid Chromatography-Mass Spectrometry (LC-MS) Retention Time (RT) of these compounds on a Xterra MS C-18 stationary phase. ANFIS and MLR methods were used as variable selection tools and a neural network was employed for predicting the RTs. Tbree descriptors of 3D-MoRSE-signal 06/weighted by atomic polarizabilities (Mor06p), Radial Distribution Function-1.0/weighted by atomic van der Waals volumes (RDF010v), and number of functional groups of R-Co-N< and > N-C=N (N-072) reveal the importance of dispersion interactions between benzodiazepines and C-18 stationary phases and also electrostatic and hydrogen bond interactions of these compounds with the polar mobile phase. The superiority of 3-4-1 ANFIS-Artificial Neural Networks (ANN) model over MLR-ANN with a linear feature selection method was illustrated by Leave-Multiple-Out (LMO) cross-validation method. Values of R2 L60=0.771 and RMSEL60=4.792 for ANFIS-ANN model should be compared with the values of R2 L60 = 0.632 and RMSEL60 = 6.481 for the MLR-ANN model. LMO-CV and Y-randomization results indicate the robustness and predictive ability of the generated model of ANFIS-ANN and show the ability of ANFIS in selecting the features for phenomena with nonlinear characteristics. Sequential Zeroing of Weights (SZW) as a sensitivity analysis method showed the importance of dispersion interaction in the retention mechanism of benzodiazepines in LC method. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
  6. Keywords:
  7. 7 aminoflunitrazepam ; Acetamidoclonazepam ; Acetamidonitrazepam ; Alprazolam ; Aminoclonazepam ; benzodiazepine derivative ; Bromazepam ; Brotizolam ; Clobazam ; Clonazepam ; Desalkyflurazepam ; Diazepam ; Drug metabolite ; Ethylflurazepam ; Flunitrazepam ; Flurazepam ; Loprazolam ; Lorazepam ; Lormetazepam ; Midazolam ; Nitrazepam ; Norclobazam ; Nordazepam ; Norflunitrazepam ; Oxazepam ; Temazepam ; Triazolam ; Unclassified drug ; Zolpidem ; Zopiclone ; Artificial neural network ; Computer prediction ; Controlled study ; Drug retention ; Fuzzy system ; Hydrogen bond ; Liquid chromatography ; Mass spectrometry ; Multiple linear regression analysis ; Priority journal ; Quantitative structure activity relation ; Sensitivity analysis
  8. Source: QSAR and Combinatorial Science ; Volume 27, Issue 4 , 2008 , Pages 407-416 ; 1611020X (ISSN)
  9. URL: https://onlinelibrary.wiley.com/doi/10.1002/qsar.200630163