We have located links that may give you full text access.
DFT-Based QSAR Modelling of Inhibitory Activity of Coumarins and Sulfocoumarins on Carbonic Anhydrase (CA) Isoforms (CA I and CA II).
Current Computer-aided Drug Design 2018 December 11
OBJECTIVE: We present three robust, validated and statistically significant quantitative structure-activity relationship (QSAR) models, which deal with the calculated molecular descriptors and experimental inhibition constant (Ki) of 42 coumarin and sulfocoumarin derivatives measured against CA I and II isoforms.
METHOD: The compounds were subjected to DFT calculations in order to obtain quantum chemical molecular descriptors. Multiple linear regression algorithm was applied to construct QSAR models. Separation of the compounds into training and test sets was accomplished using Kennard-Stone algorithm. Leverage approach was applied to determine applicability domain (AD) of the obtained models.
RESULTS: Three models were developed. The first model, CAI_model1 comprises 30/11 training/test compounds with the statistical parameters of R2=0.85, Q2=0.77, F=27.57, R2(test) =0.72. The second one, CAII_model2 comprises 30/12 training/test compounds with the statistical parameters of R2=0.86, Q2=0.78, F=30.27, R2(test) =0.85. The final model, ΔpKi_model3 consists of 25/3 training/test compounds with the statistical parameters of R2=0.78, Q2=0.62, F=13.80, R2(test) =0.99.
CONCLUSION: Interpretation of reactivity-related descriptors such as HOMO-1 and LUMO energies and visual inspection of their maps of orbital electron density lead to a conclusion that the binding free energy of the entire binding process may be modulated by the kinetics of the hydrolyzing step of coumarins.
METHOD: The compounds were subjected to DFT calculations in order to obtain quantum chemical molecular descriptors. Multiple linear regression algorithm was applied to construct QSAR models. Separation of the compounds into training and test sets was accomplished using Kennard-Stone algorithm. Leverage approach was applied to determine applicability domain (AD) of the obtained models.
RESULTS: Three models were developed. The first model, CAI_model1 comprises 30/11 training/test compounds with the statistical parameters of R2=0.85, Q2=0.77, F=27.57, R2(test) =0.72. The second one, CAII_model2 comprises 30/12 training/test compounds with the statistical parameters of R2=0.86, Q2=0.78, F=30.27, R2(test) =0.85. The final model, ΔpKi_model3 consists of 25/3 training/test compounds with the statistical parameters of R2=0.78, Q2=0.62, F=13.80, R2(test) =0.99.
CONCLUSION: Interpretation of reactivity-related descriptors such as HOMO-1 and LUMO energies and visual inspection of their maps of orbital electron density lead to a conclusion that the binding free energy of the entire binding process may be modulated by the kinetics of the hydrolyzing step of coumarins.
Full text links
Related Resources
Trending Papers
Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses and Management.International Journal of Molecular Sciences 2024 April 13
Executive Summary: State-of-the-Art Review: Unintended Consequences: Risk of Opportunistic Infections Associated with Long-term Glucocorticoid Therapies in Adults.Clinical Infectious Diseases 2024 April 11
Clinical practice guidelines on the management of status epilepticus in adults: A systematic review.Epilepsia 2024 April 13
Finerenone: From the Mechanism of Action to Clinical Use in Kidney Disease.Pharmaceuticals 2024 March 27
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app