Generation of Non-Nucleotide CD73 Inhibitors Using a Molecular Docking and 3D-QSAR Approach
Abstract
:1. Introduction
2. Results and Discussion
2.1. Molecular Docking
2.2. 3D-QSAR
Validation of 3D-QSAR Models
2.3. Contour Map Analysis
2.3.1. CoMFA Contour Maps
2.3.2. CoMSIA Contour Maps
2.4. Designing New CD73 Inhibitors
3. Materials and Methods
3.1. Training Set/Test Set Selection for 3D-QSAR Analyses
3.2. Molecular Docking
3.3. Receptor-Based CoMFA and CoMSIA Models
3D-QSAR Model Validation
3.4. Design of New CD73 Inhibitors and ADMET Calculation
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | Full Model | Test Set 5 | ||
---|---|---|---|---|
CoMFA | CoMSIA (SHAD) | CoMFA | CoMSIA (SHAD) | |
q2 | 0.763 | 0.760 | 0.844 | 0.804 |
ONC | 5 | 6 | 5 | 4 |
SEP | 0.635 | 0.646 | 0.525 | 0.581 |
r2 | 0.915 | 0.943 | 0.947 | 0.954 |
SEE | 0.380 | 0.314 | 0.306 | 0.282 |
F value | 108.134 | 134.938 | 129.146 | 191.403 |
LOF | - | - | 0.848 | 0.771 |
BS-r2 | - | - | 0.968 | 0.961 |
BS-SD | - | - | 0.012 | 0.012 |
Q2 | - | - | 0.626 | 0.599 |
r2pred | - | - | 0.698 | 0.757 |
Compound | R1 | R2 | R3 | R4 | Predicted pIC50 |
---|---|---|---|---|---|
D5 | | | | | 7.603 |
D6 | | 7.540 | |||
D8 | | | 7.645 | ||
D11 | | 8.056 | |||
D12 | | 8.134 | |||
D15 | | | 7.769 | ||
D20 | | | | 7.839 | |
D24 | | 8.088 | |||
D33 | | | | 8.047 | |
D45 | | | 8.236 | ||
D50 | | | 8.112 |
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Bhujbal, S.P.; Hah, J.-M. Generation of Non-Nucleotide CD73 Inhibitors Using a Molecular Docking and 3D-QSAR Approach. Int. J. Mol. Sci. 2021, 22, 12745. https://doi.org/10.3390/ijms222312745
Bhujbal SP, Hah J-M. Generation of Non-Nucleotide CD73 Inhibitors Using a Molecular Docking and 3D-QSAR Approach. International Journal of Molecular Sciences. 2021; 22(23):12745. https://doi.org/10.3390/ijms222312745
Chicago/Turabian StyleBhujbal, Swapnil P., and Jung-Mi Hah. 2021. "Generation of Non-Nucleotide CD73 Inhibitors Using a Molecular Docking and 3D-QSAR Approach" International Journal of Molecular Sciences 22, no. 23: 12745. https://doi.org/10.3390/ijms222312745