Dipeptidyl Peptidase 4 Inhibitors in Type 2 Diabetes Mellitus Management: Pharmacophore Virtual Screening, Molecular Docking, Pharmacokinetic Evaluations, and Conceptual DFT Analysis
Abstract
:1. Introduction
2. Materials and Methods
3. Results
4. Workflow Applicability and Future Research Direction
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Database | No of Molecules | Alogliptin (Molecules “Hits”) | Sitagliptin (Molecules “Hits”) | Linagliptin (Molecules “Hits”) |
---|---|---|---|---|
MolPot | 4,807,813 | 107 | 83 | 4 |
CHEMBL30 | 1,998,181 | 138 | 55 | 8 |
ChemDiv(2015) | 1,456,120 | 16 | 8 | 1 |
ChemSpace | 50,181,678 | 326 | 413 | 1 |
MCULE | 45,257,086 | 190 | 718 | 1 |
MCULE-ULTIMATE | 126,471,502 | 178 | 14 | 2 |
LabNetwork | 1,794,286 | 58 | 11 | 2 |
ZINC | 12,921,916 | 154 | 328 | 5 |
TOTAL | 244,888,582 | 1109 | 1619 | 24 |
(A) | |||||
CSC076365308 | ZINC95941402 | ZINC408512952 | CSC079167462 | Alogliptin | |
MW | 357.210 | 385.220 | 327.120 | 343.180 | 339.170 |
Volume | 372.349 | 387.613 | 323.978 | 365.066 | 345.687 |
Density | 0.959 | 0.994 | 1.010 | 0.940 | 0.981 |
nHA | 6 | 9 | 7 | 5 | 7 |
nHD | 2 | 4 | 1 | 3 | 2 |
nRot | 7 | 6 | 5 | 9 | 3 |
nRing | 3 | 3 | 3 | 2 | 3 |
MaxRing | 10 | 6 | 9 | 6 | 6 |
nHet | 6 | 9 | 7 | 5 | 7 |
fChar | 0 | 0 | 0 | 0 | 0 |
nRig | 18 | 20 | 18 | 13 | 21 |
Flexibility | 0.389 | 0.300 | 0.278 | 0.692 | 0.143 |
Stereo Centers | 1 | 2 | 1 | 2 | 1 |
TPSA | 74.690 | 131.050 | 92.620 | 78.790 | 97.050 |
logS | −1.511 | −1.832 | −2.903 | −2.535 | −2.103 |
logP | 1.740 | 0.78 | 1.63 | 2.128 | 1.185 |
logD | 1.714 | 1.619 | 1.497 | 2.508 | 1.452 |
PAINS | 0 alerts | 0 alerts | 0 alerts | 0 alerts | 0 alerts |
Lipinski Rule | Accepted | Accepted | Accepted | Accepted | Accepted |
Pfizer Rule | Accepted | Accepted | Accepted | Accepted | Accepted |
Npscore | −1.407 | −0.929 | −1.042 | −0.482 | −1.318 |
QED | 0.820 | 0.693 | 0.828 | 0.685 | 0.873 |
CG4 | −11.248 | −10.904 | −10.783 | −10.470 | −10.404 |
(B) | |||||
ZINC305224681 | CSC092194469 | ZINC12327733 | ZINC71876485 | Sitagliptin | |
MW | 331.050 | 316.160 | 351.140 | 317.190 | 407.120 |
Volume | 291.848 | 329.958 | 342.472 | 328.881 | 343.983 |
Density | 1.134 | 0.958 | 1.025 | 0.964 | 1.184 |
nHA | 4 | 4 | 3 | 4 | 6 |
nHD | 2 | 3 | 2 | 1 | 2 |
nRot | 5 | 7 | 4 | 5 | 6 |
nRing | 2 | 2 | 3 | 3 | 3 |
MaxRing | 6 | 6 | 6 | 6 | 9 |
nHet | 8 | 5 | 6 | 5 | 12 |
fChar | 0 | 0 | 0 | 0 | 0 |
nRig | 14 | 13 | 18 | 17 | 17 |
Flexibility | 0.357 | 0.538 | 0.222 | 0.294 | 0.353 |
Stereo Centers | 1 | 2 | 1 | 1 | 1 |
TPSA | 66.400 | 61.360 | 43.700 | 41.290 | 77.040 |
logS | −3.063 | −4.277 | −3.219 | −1.797 | −0.783 |
logP | 2.518 | 3.453 | 2.664 | 2.314 | 0.694 |
logD | 2.406 | 3.831 | 2.872 | 2.223 | 1.932 |
PAINS | 0 alerts | 0 alerts | 0 alerts | 0 alerts | 0 alerts |
Lipinski Rule | Accepted | Accepted | Accepted | Accepted | Accepted |
Pfizer Rule | Accepted | Rejected | Accepted | Accepted | Accepted |
Npscore | −1.854 | −1.260 | −0.950 | −1.884 | −1.404 |
QED | 0.882 | 0.791 | 0.890 | 0.922 | 0.672 |
CG4 | −11.107 | −10.968 | −10.712 | −10.540 | −10.500 |
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Istrate, D.; Crisan, L. Dipeptidyl Peptidase 4 Inhibitors in Type 2 Diabetes Mellitus Management: Pharmacophore Virtual Screening, Molecular Docking, Pharmacokinetic Evaluations, and Conceptual DFT Analysis. Processes 2023, 11, 3100. https://doi.org/10.3390/pr11113100
Istrate D, Crisan L. Dipeptidyl Peptidase 4 Inhibitors in Type 2 Diabetes Mellitus Management: Pharmacophore Virtual Screening, Molecular Docking, Pharmacokinetic Evaluations, and Conceptual DFT Analysis. Processes. 2023; 11(11):3100. https://doi.org/10.3390/pr11113100
Chicago/Turabian StyleIstrate, Daniela, and Luminita Crisan. 2023. "Dipeptidyl Peptidase 4 Inhibitors in Type 2 Diabetes Mellitus Management: Pharmacophore Virtual Screening, Molecular Docking, Pharmacokinetic Evaluations, and Conceptual DFT Analysis" Processes 11, no. 11: 3100. https://doi.org/10.3390/pr11113100