Discovery of Novel HIV Protease Inhibitors Using Modern Computational Techniques
Abstract
:1. Introduction
2. Results and Discussion
2.1. Pharmacophore Annotation and Similarity Search
2.2. Physicochemical Properties Evaluation
2.3. Molecular Docking Studies
2.4. Anti-HIV Prediction Analysis
2.5. ADMET Analysis
2.5.1. Absorption and Distribution Evaluations
2.5.2. Metabolism and Excretion
2.5.3. Toxicity Analysis
3. Materials and Methods
3.1. Database
3.2. Physicochemical Evaluation for Drug-Likeness
3.3. ADMET Predictions
3.4. Pharmacophore Generation and Similarity Search
3.5. Molecular Docking (MOE, 2020) [49]
3.6. Prediction of HIV Activity
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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S/N | Comp Code | MW | a_don | a_acc | b_1rotN | logP(o/w) | TPSA Ų | % ABS |
---|---|---|---|---|---|---|---|---|
1 | HPS/001 | 632.78 | 5 | 4 | 15 | 4.97 | 120.00 | 67.60 |
2 | HPS/002 | 642.80 | 6 | 4 | 15 | 4.69 | 137.07 | 61.71 |
3 | HPS/003 | 632.78 | 5 | 4 | 16 | 4.43 | 120.00 | 67.60 |
4 | HPS/004 | 642.80 | 6 | 4 | 15 | 4.69 | 137.07 | 61.71 |
5 | Lopinavir | 628.814 | 5 | 4 | 15 | 5.19 | 120.00 | 67.60 |
6 | HPS/005 | 720.98 | 3 | 5 | 19 | 4.58 | 129.99 | 64.15 |
7 | HPS/006 | 698.93 | 3 | 6 | 18 | 3.09 | 139.22 | 60.97 |
8 | HPS/007 | 700.95 | 3 | 6 | 18 | 3.06 | 139.22 | 60.97 |
9 | HPS/008 | 676.91 | 3 | 5 | 18 | 4.67 | 125.55 | 65.69 |
10 | Ritonavir | 720.96 | 4 | 6 | 18 | 5.00 | 145.78 | 58.71 |
11 | HPS/009 | 519.66 | 5 | 3 | 14 | 2.83 | 131.19 | 63.74 |
12 | HPS/010 | 505.64 | 5 | 3 | 13 | 2.39 | 131.19 | 63.74 |
13 | HPS/011 | 505.64 | 5 | 3 | 13 | 2.39 | 131.19 | 63.74 |
14 | HPS/012 | 531.67 | 5 | 3 | 13 | 2.78 | 131.19 | 63.74 |
15 | Fosamprenavir | 583.60 | 5 | 2 | 13 | 1.40 | 171.40 | 49.87 |
16 | HPS/013 | 489.64 | 4 | 2 | 13 | 3.40 | 110.96 | 70.72 |
17 | HPS/014 | 489.64 | 4 | 2 | 13 | 3.40 | 110.96 | 70.72 |
18 | HPS/015 | 462.59 | 3 | 2 | 13 | 3.07 | 124.79 | 65.95 |
19 | HPS/016 | 490.62 | 5 | 2 | 13 | 3.06 | 105.17 | 72.72 |
20 | Amprenavir | 505.64 | 5 | 3 | 11 | 2.39 | 131.19 | 63.74 |
21 | HPS/017 | 465.64 | 4 | 2 | 12 | 1.71 | 120.74 | 67.34 |
22 | HPS/018 | 574.73 | 6 | 4 | 14 | 3.56 | 131.48 | 63.64 |
23 | HPS/019 | 532.69 | 3 | 2 | 14 | 4.48 | 133.23 | 63.03 |
24 | HPS/020 | 575.71 | 6 | 4 | 17 | 3.49 | 132.89 | 63.15 |
25 | Atazanavir | 704.87 | 7 | 5 | 14 | 4.74 | 171.22 | 49.93 |
26 | HPS/021 | 573.71 | 6 | 3 | 13 | 2.70 | 126.43 | 65.38 |
27 | HPS/022 | 595.72 | 6 | 3 | 13 | 3.37 | 140.42 | 60.56 |
28 | HPS/023 | 574.72 | 6 | 2 | 14 | 2.84 | 117.41 | 68.49 |
29 | HPS/024 | 546.66 | 5 | 2 | 12 | 2.49 | 145.46 | 58.81 |
30 | Darunavir | 547.70 | 3 | 9 | 12 | 2.9 | 149 | 51.41 |
31 | HPS/025 | 645.89 | 7 | 3 | 14 | 5.01 | 125.04 | 65.86 |
32 | HPS/026 | 661.89 | 8 | 4 | 14 | 4.86 | 145.27 | 59.92 |
33 | HPS/027 | 661.89 | 8 | 4 | 14 | 4.86 | 145.27 | 59.92 |
34 | HPS/028 | 569.81 | 6 | 5 | 12 | 5.35 | 105.06 | 72.75 |
35 | Nelfinavir | 547.673 | 6 | 3 | 11 | 2.436 | 140.42 | 60.56 |
Ref Drug | S/N | Comp Code | ΔG (kcal/mol) | IC50 (µM) | % Inhibition |
---|---|---|---|---|---|
Lopinavir | 1 | HPS/001 | −8.28 | 304.89 | 90.15 |
2 | HPS/002 | −8.24 | 48.9 | 90.13 | |
3 | HPS/003 | −7.91 | 318.74 | 82.65 | |
4 | HPS/004 | −7.88 | 48.9 | 90.13 | |
5 | Lopinavir | −7.80 | 203.69 | 90.12 | |
Ritonavir | 6 | HPS/005 | −8.98 | 7.79 | 59.07 |
7 | HPS/006 | −8.63 | 31.17 | 59.8 | |
8 | HPS/007 | −8.57 | 36.33 | 60.78 | |
9 | HPS/008 | −8.54 | 14.58 | 59.48 | |
10 | Ritonavir | −8.35 | 24.99 | 53.74 | |
Fosamprenavir | 11 | HPS/009 | −7.31 | −14.7 | 65.58 |
12 | HPS/010 | −7.15 | 6.80 | 65.59 | |
13 | HPS/011 | −6.97 | 6.80 | 65.59 | |
14 | HPS/012 | −6.91 | −16.04 | 65.57 | |
15 | Fosamprenavir | −6.88 | 39.79 | 65.65 | |
Amprenavir | 16 | HPS/013 | −6.96 | 0.14 | 54.98 |
17 | HPS/014 | −6.85 | 0.14 | 54.98 | |
18 | HPS/015 | −6.76 | 134.14 | 70.70 | |
19 | HPS/016 | −6.72 | 66.22 | 66.11 | |
20 | Amprenavir | −6.69 | 6.8 | 65.59 | |
Atazanavir | 21 | HPS/017 | −8.09 | 28.40 | 59.85 |
22 | HPS/018 | −7.87 | −18.12 | 52.71 | |
23 | HPS/019 | −7.68 | 168.45 | 54.00 | |
24 | HPS/020 | −7.64 | −2.52 | 56.87 | |
25 | Atazanavir | −7.63 | 7.88 | 52.48 | |
Darunavir | 26 | HPS/021 | −8.00 | 50.02 | 61.53 |
27 | HPS/022 | −7.50 | 28.2 | 58.64 | |
28 | HPS/023 | −7.28 | 1.38 | 61.04 | |
29 | HPS/024 | −7.29 | −18.51 | 58.39 | |
30 | Darunavir | −7.01 | −0.3 | 55.17 | |
Nelfinavir | 31 | HPS/025 | −7.94 | −3.48 | 50.47 |
32 | HPS/026 | −7.84 | 28.4 | 58.79 | |
33 | HPS/027 | −7.60 | 4.92 | 58.79 | |
34 | HPS/028 | −7.59 | 1.78 | 56.16 | |
35 | Nelfinavir | −7.58 | 9.51 | 50.47 |
S/N | Compound | Ligand | Receptor | Interaction | Distance (Å) | E (kcal/mol) |
---|---|---|---|---|---|---|
1 | HPS/002 | O 1 | O GLY 27 | H-donor | 2.94 | −1.9 |
C 21 | O GLY 27 | H-donor | 3.21 | −0.2 | ||
C 58 | OD2 ASP 30 | H-donor | 3.60 | −0.2 | ||
O 6 | N ASP 29 | H-acceptor | 2.94 | −1.6 | ||
6-ring | CA GLY 27 | pi-H | 4.28 | −0.2 | ||
6-ring | CG1 ILE 50 | pi-H | 4.24 | −0.4 | ||
2 | HPS/004 | C 21 | O GLY 27 | H-donor | 3.52 | −0.2 |
O 3 | N ILE 50 | H-acceptor | 3.37 | −0.8 | ||
O 6 | N ASP 29 | H-acceptor | 3.22 | −2.4 | ||
6-ring | CA ILE 47 | pi-H | 4.54 | −0.2 | ||
6-ring | N GLY 48 | pi-H | 3.85 | −1.2 | ||
3 | HPS/006 | S 1 | OG1 THR80 | H-donor | 3.73 | −1.2 |
N 10 | O GLY 27 | H-donor | 3.69 | −0.2 | ||
C 29 | OD1 ASP 25 | H-donor | 3.12 | −2.6 | ||
S 1 | CD1 ILE 54 | H-acceptor | 4.11 | −0.2 | ||
O 4 | CA GLY 49 | H-acceptor | 3.30 | −0.6 | ||
4 | HPS/007 | N 8 | O ILE 50 | H-donor | 2.83 | −9.6 |
C 37 | O GLY 52 | H-donor | 3.13 | −0.7 | ||
C 68 | OG1 THR80 | H-donor | 3.44 | −0.2 | ||
C 75 | OD2 ASP 25 | H-donor | 3.32 | −0.3 | ||
S 2 | CD1 ILE 50 | H-acceptor | 4.27 | −0.2 | ||
6-ring | CD1 LEU 23 | pi-H | 4.41 | −0.2 | ||
6-ring | CD2 LEU 23 | pi-H | 3.88 | −0.3 | ||
5-ring | CD1 LEU 47 | pi-H | 3.72 | −0.4 | ||
5 | HPS/008 | S 2 | OD2 ASP 29 | H-donor | 3.54 | −3.2 |
S 2 | OD1 ASP 30 | H-donor | 3.47 | −0.2 | ||
N 7 | O GLY 27 | H-donor | 3.41 | −0.6 | ||
N 9 | O GLY 48 | H-donor | 3.13 | −0.6 | ||
C 33 | O GLY 27 | H-donor | 3.36 | −0.2 | ||
N 15 | NZ LYS 45 | H-acceptor | 3.30 | −2.8 | ||
6-ring | CD1 ILE 47 | pi-H | 4.18 | −0.8 | ||
6-ring | N ILE 50 | pi-H | 3.92 | −1.0 | ||
6 | HPS/009 | C 36 | O GLY 27 | H-donor | 3.61 | −0.3 |
O 7 | N ASP 29 | H-acceptor | 3.05 | −1.9 | ||
6-ring | CA GLY 27 | pi-H | 3.63 | −0.6 |
Absorption | Distribution | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
S/N | Comp Code | Water Solubility | Caco2 Perm | Intestine Abs | Skin Perm. | P-GPS | P-GP1I | P-GP2I | VDss | FU | BBB Perm. | CNS Perm. |
1 | HPS/001 | −4.788 | −0.162 | 60.891 | −2.735 | Yes | Yes | Yes | −0.362 | 0 | −1.011 | −3.069 |
2 | HPS/002 | −4.625 | 0.271 | 61.515 | −2.735 | Yes | Yes | Yes | −0.399 | −0.399 | −0.712 | −3.11 |
3 | HPS/003 | −4.741 | −0.246 | 71.033 | −2.735 | Yes | Yes | Yes | −0.31 | 0.019 | −1.35 | −3.154 |
4 | HPS/004 | −4.625 | 0.271 | 61.515 | 61.515 | Yes | Yes | Yes | −0.399 | 0.012 | −0.712 | −3.11 |
5 | Lopinavir | −2.892 | 1.497 | 76.395 | −2.735 | No | No | No | 0.011 | 0.381 | −1.525 | −1.418 |
6 | HPS/005 | −3.84 | 0.216 | 70.919 | −2.735 | Yes | Yes | Yes | 0.702 | 0 | −1.76 | −3.362 |
7 | HPS/006 | −4.11 | 0.737 | 71.415 | −2.735 | Yes | Yes | Yes | 0.302 | 0.048 | −1.844 | −3.642 |
8 | HPS/007 | −3.209 | 0.464 | 69.849 | −2.735 | Yes | Yes | Yes | 1.105 | 1.105 | −1.789 | −3.895 |
9 | HPS/008 | −4.232 | 0.561 | 79.662 | −2.735 | Yes | Yes | Yes | 0.273 | 0 | −1.678 | −3.23 |
10 | Ritonavir | −3.358 | 0.377 | 69.45 | −2.735 | Yes | Yes | Yes | 0.429 | 0 | −1.665 | −3.295 |
11 | HPS/009 | −3.315 | 0.356 | 66.625 | −2.741 | Yes | Yes | No | 0.639 | 0.093 | −1.081 | −3.461 |
12 | HPS/010 | −3.312 | 0.354 | 65.884 | −2.742 | Yes | Yes | No | 0.552 | 0.079 | −1.018 | −3.473 |
13 | HPS/011 | −3.312 | 0.354 | 65.884 | −2.742 | Yes | Yes | No | 0.552 | 0.079 | −1.018 | −3.473 |
14 | HPS/012 | −3.499 | 0.484 | 71.755 | −2.74 | Yes | Yes | No | 0.603 | 0.03 | −0.974 | −3.413 |
15 | Fosamprenavir | −3.239 | 0.201 | 76.433 | −2.735 | Yes | Yes | No | 0.228 | 0.12 | −1.816 | −4.025 |
16 | HPS/013 | −3.631 | 0.467 | 81.852 | −2.746 | Yes | Yes | No | 0.569 | 0.012 | −0.919 | −2.991 |
17 | HPS/014 | −3.631 | 0.467 | 81.852 | −2.746 | Yes | Yes | No | 0.569 | 0.012 | −0.919 | −2.991 |
18 | HPS/015 | −3.494 | −0.099 | 65.218 | −2.735 | Yes | No | No | −0.556 | 0.089 | −1.022 | −3.197 |
19 | HPS/016 | −4.52 | 0.613 | 73.02 | −2.812 | Yes | Yes | No | 0.127 | 0 | −1.033 | −3.333 |
20 | Amprenavir | −3.312 | 0.354 | 65.884 | −2.742 | Yes | Yes | No | 0.552 | 0.079 | −1.018 | −3.473 |
21 | HPS/017 | −3.028 | 0.394 | 74.785 | −2.755 | Yes | Yes | Yes | 1.614 | 0.361 | −0.792 | −2.976 |
22 | HPS/018 | −3.511 | −0.247 | 63.672 | −2.735 | Yes | Yes | Yes | 0.325 | 0.107 | −1.222 | −3.158 |
23 | HPS/019 | −3.278 | −0.116 | 46.777 | −2.735 | Yes | No | Yes | 0.143 | 0.222 | −0.925 | −2.715 |
24 | HPS/020 | −4.316 | 0.288 | 60.286 | −2.741 | Yes | Yes | Yes | 0.053 | 0.05 | −0.964 | −3.071 |
25 | Atazanavir | −3.849 | 0.294 | 45.728 | −2.735 | Yes | Yes | Yes | 0.143 | 0.03 | −1.352 | −3.224 |
26 | HPS/021 | −3.381 | 0.457 | 80.889 | −2.725 | Yes | Yes | No | 0.776 | 0.046 | −1.076 | −3.474 |
27 | HPS/022 | −3.796 | 0.358 | 82.453 | −2.735 | Yes | Yes | Yes | 0.208 | 0 | −1.115 | −3.273 |
28 | HPS/023 | −3.401 | 0.51 | 79.453 | −2.738 | Yes | Yes | Yes | 0.148 | 0.242 | −1.15 | −3.47 |
29 | HPS/024 | −3.289 | −3.289 | 49.063 | −2.735 | Yes | No | No | 0.06 | 0.164 | −0.921 | −3.656 |
30 | Darunavir | −3.348 | 0.493 | 75.477 | −2.739 | Yes | Yes | No | −2.739 | 0.055 | −1.111 | −3.519 |
31 | HPS/025 | −4.568 | 0.777 | 69.402 | −2.73 | Yes | Yes | Yes | 0.129 | 0.052 | −0.935 | −2.849 |
32 | HPS/026 | −3.711 | 0.265 | 66.903 | −2.735 | Yes | Yes | Yes | 0.31 | 0.139 | −1.099 | −2.911 |
33 | HPS/027 | −3.711 | 0.265 | 66.903 | −2.735 | Yes | Yes | Yes | 0.31 | 0.139 | −1.099 | −2.911 |
34 | HPS/028 | −3.107 | 0.575 | 70.605 | −2.735 | Yes | Yes | Yes | 0.831 | 0.294 | −0.77 | −2.498 |
35 | Nelfinavir | −3.894 | 0.693 | 70.888 | −2.737 | Yes | Yes | Yes | 0.563 | 0.094 | −0.522 | −2.245 |
Metabolism | Excretion | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
S/N | Comp Code | CYP2D6 Substrate | CYP3A4 Substrate | CYP1A2 Inhibitor | CYP2C19 Inhibitor | CYP2C9 Inhibitor | CYP2D6 Inhibitor | CYP3A4 Inhibitor | Total Clearance (log ml/min/kg) | Renal OCT2 Substrate |
1 | HPS/001 | No | Yes | No | Yes | No | No | Yes | 0.335 | No |
2 | HPS/002 | No | Yes | No | No | No | No | Yes | 0.429 | Yes |
3 | HPS/003 | No | Yes | No | Yes | Yes | No | Yes | 0.371 | No |
4 | HPS/004 | No | Yes | No | No | No | No | Yes | 0.429 | No |
5 | Lopinavir | No | No | Yes | No | No | No | No | −114.036 | No |
6 | HPS/005 | No | Yes | No | No | Yes | No | Yes | 0.613 | No |
7 | HPS/006 | No | Yes | No | No | No | No | Yes | 1.122 | No |
8 | HPS/007 | No | Yes | No | No | No | No | Yes | 1.202 | No |
9 | HPS/008 | No | Yes | No | Yes | Yes | No | Yes | 0.374 | No |
10 | Ritonavir | No | Yes | No | No | Yes | No | Yes | 0.564 | No |
11 | HPS/009 | No | Yes | No | No | No | No | Yes | 1.021 | No |
12 | HPS/010 | No | Yes | No | No | No | No | Yes | 0.918 | No |
13 | HPS/011 | No | Yes | No | No | No | No | Yes | 0.918 | No |
14 | HPS/012 | No | Yes | No | No | No | No | Yes | 0.755 | No |
15 | Fosamprenavir | No | Yes | No | No | No | No | Yes | 0.282 | No |
16 | HPS/013 | No | Yes | No | Yes | Yes | No | Yes | 0.782 | No |
17 | HPS/014 | No | Yes | No | Yes | Yes | No | Yes | 0.782 | No |
18 | HPS/015 | No | No | No | No | No | No | No | 1.06 | No |
19 | HPS/016 | No | Yes | No | Yes | No | No | Yes | 1.13 | No |
20 | Amprenavir | No | Yes | No | No | No | No | Yes | 0.918 | No |
21 | HPS/017 | No | Yes | No | No | No | Yes | Yes | 0.793 | No |
22 | HPS/018 | No | Yes | No | Yes | Yes | No | Yes | 0.375 | No |
23 | HPS/019 | No | Yes | No | No | No | No | No | 0.378 | No |
24 | HPS/020 | No | Yes | No | Yes | Yes | No | Yes | 0.767 | No |
25 | Atazanavir | No | Yes | No | No | Yes | No | Yes | 0.258 | No |
26 | HPS/021 | No | Yes | No | No | No | No | Yes | 0.439 | No |
27 | HPS/022 | No | Yes | No | No | Yes | No | Yes | 0.467 | No |
28 | HPS/023 | No | Yes | No | No | No | No | Yes | 0.491 | No |
29 | HPS/024 | No | Yes | No | No | No | No | No | 0.654 | No |
30 | Darunavir | No | Yes | No | No | No | No | Yes | 0.622 | No |
31 | HPS/025 | No | Yes | No | No | No | No | Yes | 0.439 | No |
32 | HPS/026 | No | Yes | No | No | No | No | Yes | −0.117 | No |
33 | HPS/027 | No | Yes | No | No | No | No | Yes | −0.117 | No |
34 | HPS/028 | Yes | Yes | No | No | No | Yes | No | 0.447 | No |
35 | Nelfinavir | No | Yes | No | Yes | No | Yes | Yes | 0.399 | No |
S/N | Comp Code | LD50 mg/kg | Toxici-ty Class | Average Similarity | Prediction Accuracy % | Hepatotoxicity | Carcino-Genicity | Immuno-Toxicity | Muta-Genicity | Cytotoxicity | Aroma-Tase | Estrogen Receptor-α | Androgen Receptor | PPAR-γ |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | HPS/001 | 5000 | V | 61.43 | 68.07 | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a |
2 | HPS/002 | 5000 | V | 58.87 | 67.38 | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a |
3 | HPS/003 | 5000 | V | 61.99 | 68.07 | Inactive a | Inactive | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a |
4 | HPS/004 | 5000 | V | 58.87 | 67.38 | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a |
5 | Lopinavir | 5000 | V | 59.88 | 67.38 | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a | Inactive a |
6 | HPS/005 | 1000 | IV | 40.75 | 54.26 | Active | Inactive | Inactive | Inactive | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
7 | HPS/006 | 800 | IV | 42.36 | 54.26 | Inactive | Inactive | Inactive a | Inactive | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
8 | HPS/007 | 1000 | IV | 42.53 | 54.26 | Inactive | Inactive | Inactive a | Inactive | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
9 | HPS/008 | 500 | IV | 40.28 | 54.26 | Inactive | Inactive | Inactive a | Inactive | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
10 | Ritonavir | 1000 | IV | 42.32 | 54.26 | Active a | Inactive | Inactive a | Inactive a | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
11 | HPS/009 | 300 | III | 48.58 | 54.26 | Inactive | Inactive | Inactive a | Inactive a | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
12 | HPS/010 | 300 | III | 48.58 | 54.26 | Inactive a | Inactive | Inactive a | Inactive a | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
13 | HPS/011 | 300 | III | 48.58 | 54.26 | Inactive a | Inactive | Inactive a | Inactive a | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
14 | HPS/012 | 300 | III | 48.12 | 54.26 | Inactive | Inactive | Inactive a | Inactive a | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
15 | Fosamprenavir | 300 | III | 43.99 | 54.26 | Inactive a | Inactive | Inactive a | Inactive | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
16 | HPS/013 | 300 | III | 50.25 | 67.38 | Inactive a | Inactive | Inactive a | Inactive a | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
17 | HPS/014 | 300 | III | 50.25 | 67.38 | Inactive a | Inactive | Inactive a | Inactive a | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
18 | HPS/015 | 2500 | V | 51.48 | 67.38 | Inactive | Inactive | Inactive a | Inactive a | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
19 | HPS/016 | 1000 | IV | 48.28 | 54.26 | Inactive a | Inactive | Inactive a | Inactive a | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
20 | Amprenavir | 300 | III | 48.58 | 54.26 | Inactive a | Inactive | Inactive a | Inactive a | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
21 | HPS/017 | 200 | III | 47.45 | 54.26 | Active | Active | Active a | Inactive | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
22 | HPS/018 | 200 | III | 44.60 | 54.26 | Inactive | Inactive | Inactive a | Inactive | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
23 | HPS/019 | 500 | IV | 60.36 | 68.07 | Inactive | Inactive | Inactive a | Inactive a | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
24 | HPS/020 | 200 | III | 48.94 | 54.26 | Inactive | Inactive | Inactive a | Inactive | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
25 | Atazanavir | 200 | III | 47.65 | 54.26 | Active | Inactive | Inactive a | Inactive | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
26 | HPS/021 | 245 | III | 48.68 | 54.26 | Active | Inactive | Active | Inactive | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
27 | HPS/022 | 245 | III | 48 | 54.26 | Active | Inactive | Active | Inactive | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
28 | HPS/023 | 245 | III | 50.43 | 67.38 | Active | Active | Active | Inactive | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
29 | HPS/024 | 3000 | V | 47.04 | 54.26 | Active | Inactive | Inactive a | Inactive | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
30 | Darunavir | 245 | III | 52.42 | 67.38 | Active a | Inactive | Inactive | Inactive | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
31 | HPS/025 | 1000 | IV | 45.27 | 54.26 | Inactive | Inactive | Active a | Inactive | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
32 | HPS/026 | 1000 | IV | 43.19 | 54.26 | Inactive | Inactive | Active a | Inactive | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
33 | HPS/027 | 1000 | IV | 43.19 | 54.26 | Inactive | Inactive | Active a | Inactive | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
34 | HPS/028 | 1000 | IV | 45.52 | 54.26 | Inactive | Inactive | Active a | Inactive a | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
35 | Nelfinavir | 600 | IV | 49.30 | 54.26 | Inactive | Inactive | Active a | Inactive a | Inactive | Inactive a | Inactive a | Inactive a | Inactive a |
S/N | Comp Code | AMES Toxicity | Max. Tolerated Dose (Human) | hERG I Inhibitor | hERG II Inhibitor | (LD50) mol/kg | (LOAEL) log mg/kg_bw/day | Hepatotoxicity | Skin Sensitization | T.Pyriformis Toxicity | Minnow Toxicity |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | HPS/001 | No | −0.272 | No | Yes | 2.413 | 3.504 | Yes | No | 0.286 | −1.564 |
2 | HPS/002 | No | −0.254 | No | Yes | 2.38 | 2.979 | Yes | No | 0.285 | −1.219 |
3 | HPS/003 | No | −0.198 | No | Yes | 2.8 | 3.389 | Yes | No | 0.285 | −2.213 |
4 | HPS/004 | No | −0.254 | No | Yes | 2.674 | 3.842 | Yes | No | 0.285 | −1.219 |
5 | Lopinavir | No | −0.297 | No | Yes | 2.382 | 5.949 | Yes | No | 0.286 | −1.501 |
6 | HPS/005 | No | −0.22 | No | Yes | 2.818 | 3.631 | Yes | No | 0.285 | 4.55 |
7 | HPS/006 | No | −0.224 | No | Yes | 3.206 | 2.454 | Yes | No | 0.285 | 1.04 |
8 | HPS/007 | No | −0.3 | No | Yes | 2.714 | 2.126 | Yes | No | 0.285 | 1.197 |
9 | HPS/008 | No | −0.308 | No | Yes | 2.661 | 2.169 | Yes | No | 0.286 | 1.535 |
10 | Ritonavir | No | 0.096 | No | Yes | 2.703 | 2.231 | Yes | No | 0.285 | 1.787 |
11 | HPS/009 | No | 0.021 | No | No | 2.578 | 1.744 | Yes | No | 0.285 | −3.865 |
12 | HPS/010 | No | 0 | No | No | 2.617 | 1.767 | Yes | No | 0.285 | −4.033 |
13 | HPS/011 | No | 0 | No | No | 2.617 | 1.767 | Yes | No | 0.285 | −4.033 |
14 | HPS/012 | No | −0.16 | No | No | 2.69 | 1.663 | Yes | No | 0.285 | −4.327 |
15 | Fosamprenavir | No | −0.029 | No | No | 2.396 | 2.151 | Yes | No | 0.285 | −4.393 |
16 | HPS/013 | No | −0.355 | No | No | 2.415 | 1.989 | Yes | No | 0.293 | −3.9 |
17 | HPS/014 | No | −0.355 | No | No | 2.415 | 1.989 | Yes | No | 0.293 | −3.9 |
18 | HPS/015 | No | −0.29 | No | No | 2.282 | 1.904 | Yes | No | 0.285 | −1.634 |
19 | HPS/016 | No | −0.048 | No | No | 3.255 | 1.823 | Yes | No | 0.286 | −4.231 |
20 | Amprenavir | No | 0 | No | No | 2.617 | 1.767 | Yes | No | 0.285 | −4.033 |
21 | HPS/017 | Yes | −0.295 | No | Yes | 2.528 | 1.731 | Yes | No | 0.286 | 0.934 |
22 | HPS/018 | No | 0.178 | No | Yes | 2.805 | 5.592 | Yes | No | 0.285 | 1.481 |
23 | HPS/019 | No | 0.256 | No | Yes | 2.567 | 4.603 | Yes | No | 0.285 | 0.939 |
24 | HPS/020 | No | −0.419 | No | Yes | 3.317 | 0.624 | Yes | No | 0.286 | 0.553 |
25 | Atazanavir | No | −0.16 | No | No | 2.665 | 2.703 | Yes | No | 0.285 | 2.075 |
26 | HPS/021 | No | −0.914 | No | No | 2.702 | 1.716 | Yes | No | 0.29 | 0.501 |
27 | HPS/022 | No | −0.353 | No | Yes | 2.434 | 2.96 | Yes | No | 0.286 | −0.052 |
28 | HPS/023 | No | −0.504 | No | Yes | 2.088 | 2.666 | Yes | No | 0.285 | 0.463 |
29 | HPS/024 | No | −0.105 | No | No | 2.535 | 2.336 | Yes | No | 0.285 | 1.082 |
30 | Darunavir | No | −0.763 | No | No | 2.107 | 2.775 | Yes | No | 0.289 | 0.61 |
31 | HPS/025 | No | −0.831 | No | Yes | 2.566 | 2.949 | Yes | No | 0.29 | 0.501 |
32 | HPS/026 | No | −0.575 | No | Yes | 2.538 | 3.508 | Yes | No | 0.285 | 1.725 |
33 | HPS/027 | No | −0.575 | No | Yes | 2.538 | 3.508 | Yes | No | 0.285 | 1.725 |
34 | HPS/028 | No | 0.019 | No | Yes | 2.379 | 4.271 | Yes | No | 0.285 | 2.047 |
35 | Nelfinavir | No | −0.576 | No | Yes | 2.54 | 3.911 | Yes | No | 0.287 | 1.236 |
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Okafor, S.N.; Angsantikul, P.; Ahmed, H. Discovery of Novel HIV Protease Inhibitors Using Modern Computational Techniques. Int. J. Mol. Sci. 2022, 23, 12149. https://doi.org/10.3390/ijms232012149
Okafor SN, Angsantikul P, Ahmed H. Discovery of Novel HIV Protease Inhibitors Using Modern Computational Techniques. International Journal of Molecular Sciences. 2022; 23(20):12149. https://doi.org/10.3390/ijms232012149
Chicago/Turabian StyleOkafor, Sunday N., Pavimol Angsantikul, and Hashim Ahmed. 2022. "Discovery of Novel HIV Protease Inhibitors Using Modern Computational Techniques" International Journal of Molecular Sciences 23, no. 20: 12149. https://doi.org/10.3390/ijms232012149