Cube-Rhombellane Related Structures: A Drug Perspective
Abstract
:1. Introduction
2. Results
2.1. DFT Results
2.2. Bioactivity Evaluation
2.2.1. MM Computations
2.2.2. Globularity
2.2.3. ADME Properties Evaluation
2.2.4. RECAP Analysis
3. Methods
4. Discussions
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Not applicable. |
Structure | v | C | H | N | O | Table | Type I | Type II |
---|---|---|---|---|---|---|---|---|
C-rbl | 420 | 192 | 156 | 24 | 48 | 2(1) | Ether; Amide | 7:(6(6).B(3).Mt(2).8BMt(3)) |
Env (420) | 288 | 132 | 108 | 24 | 24 | 2(2) | Amide | 8:(0.0.0.8BMt(3)) |
Env (420) | 336 | 144 | 132 | 24 | 36 | 2(3) | Amide | 8:(0.0. Mt(2-OH).8BMt(3)) |
Core | 120 | 48 | 48 | 0 | 24 | 2(4) | Ether | 4:(6(6).B(3).0.0) |
Core | 108 | 48 | 48 | 0 | 12 | 2(5) | Ether | 4:(6(3).B(3).0.0) |
Core | 132 | 60 | 60 | 0 | 12 | 2(6) | Ether | 4:(6(3).6(3).0.0) |
C-rbl (4) | 264 | 132 | 84 | 0 | 48 | 2(7) | Ether; Ester | 6:((6(6).Mt(2).4B(3)) |
C-rbl (4) | 300 | 144 | 84 | 0 | 72 | 2(8) | Ether; Ester | 6:((6(6).Mt(2-COOH).4B(3)) |
Ada-C-rbl | 276 | 120 | 84 | 0 | 72 | 2(9); 3(1) | Ether | 5:(6(6).B(3).Mt(2).0) |
C-rbl | 348 | 168 | 108 | 24 | 48 | 3(2) | Ether; Amide | 7:(6(6).B(3).Mt(2).8B(3)) |
Env (348) | 264 | 120 | 84 | 24 | 36 | 3(3) | Amide | 8:(0.0.0.8B(3)) |
C-rbl | 444 | 192 | 180 | 24 | 48 | 3(4) | Ether; Amide | 7:(6(6).6(3).Mt(2).8BMt(3)) |
C-rbl | 456 | 156 | 192 | 24 | 84 | 3(5) | Ether; Amide | 7:(6(6).6(6).Mt(2).8BMt(3)) |
Formula | Total Atoms | PG | Egap (eV) | Ebind (a.u.) | Ebind/N (kcal/mol) | Etot (a.u.) | |
---|---|---|---|---|---|---|---|
1 | C192H156N24O48 | 420 | T | 4.390 | −93.497 | −222.236 | −12334.939 |
2 | C132H108N24O24 | 288 | T | 4.451 | −65.811 | −229.427 | −8215.224 |
3 | C144H132N24O36 | 336 | T | 4.965 | −73.981 | −227.568 | −9589.441 |
4 | C48H48O24 | 120 | T | 6.104 | −24.528 | −236.370 | −3663.244 |
5 | C48H48O12 | 108 | Td | 6.200 | −22.601 | −213.768 | −2760.590 |
6 | C48H72O12 | 132 | Oh | 6.139 | −24.906 | −260.481 | −2774.902 |
7 | C132H84O48 | 264 | T | 4.020 | −59.334 | −206.849 | −8690.700 |
8 | C144H84O72 | 300 | T | 3.692 | −67.266 | −195.418 | −10953.399 |
9 | C120H84O72 | 276 | T | 4.276 | −59.767 | −195.335 | −10039.276 |
10 | C12H15N3O3 | 33 | C3 | 6.282 | −6.854 | −238.962 | −856.290 |
11 | C16H22N4O6 | 48 | C2 | 5.220 | −9.666 | −233.289 | −1293.368 |
Ada−C−rbl.276 (1) | C_rbl.348 (2) | Env.264 (3) | C_rbl.444 (4) | C_rbl.456 (5) | |
---|---|---|---|---|---|
1 | 412.152 | 1876.9 | 133.294 | 754.677 | 1334.91 |
2 | 411.509 | 1888.4 | 133.281 | 770.938 | 1275.35 |
3 | 407.547 | 1872.15 | 133.086 | 776.412 | 1301.15 |
4 | 445.824 | 1931.21 | 105.310 | 793.852 | 1354.78 |
5 | 387.843 | 1916.52 | 150.839 | 778.074 | 1305.25 |
6 | 392.251 | 1858.42 | 141.293 | 820.662 | 1303.09 |
7 | 413403 | 1866.64 | 136.255 | 774.167 | 1283.52 |
8 | 421.086 | 1857.53 | 108.876 | 779.648 | 1301.57 |
9 | 435.597 | 1907.43 | 125.237 | 821.927 | 1293.61 |
10 | 439.588 | 1867.08 | 155.056 | 816.659 | 1336.80 |
Molecule | QPpolrz | QPlogPC16 | QPlogPoct | QPlogPw | QPlogKhsa | QPlogPo/w |
---|---|---|---|---|---|---|
Nanotube (5,5) | 172.56 | 40.958 | 70.161 | 14.096 | 10.553 | 23.631 |
Nanotube (3,3) | 102.772 | 25.308 | 41.65 | 6.671 | 5.881 | 13.667 |
C70 | 58.28 | 16.258 | 22.272 | 3.89 | 2.853 | 8.587 |
C60 | 50.017 | 14.398 | 18.716 | 3.444 | 2.292 | 7.599 |
C_rbl_456 (3(5) | 196.72 | 59.101 | 191.881 | 189.665 | −17.697 | −26.217 |
C_rbl_444 (3(4)) | 192.178 | 54.083 | 166.025 | 152.579 | −14.823 | −18.859 |
C_rbl_348 (3(2)) | 180.498 | 46.315 | 169.989 | 151.045 | −4.982 | −11.232 |
Ada−C−rbl_276 (3(1)) | 155.706 | 58.948 | 155.222 | 120.044 | −11.895 | −5.558 |
Env_264 (3(3)) | 152.497 | 49.581 | 157.638 | 151.739 | −12.271 | −25.591 |
Molecule | QPlogS | CIQPlogS | QPlogHERG | QPPCaco | QPlogBB | QPPMDCK | QPlogKp |
---|---|---|---|---|---|---|---|
Nanotube (5,5) | −55.716 | −55.716 | −11.271 | 9906.038 | 0.192 | 5899.293 | 3.712 |
Nanotube (3,3) | −32.425 | −32.425 | −6.455 | 9906.038 | 0.192 | 5899.293 | 1.726 |
C70 | −17.329 | −17.329 | −4.863 | 9906.038 | 0.192 | 5899.293 | 0.714 |
C60 | −14.534 | −14.534 | −4.634 | 9906.038 | 0.192 | 5899.293 | 0.517 |
C_rbl_456 (Tb3(5) | 2 | −6.18 | 29.537 | 0 | −13.489 | 0.002 | 0.76 |
C_rbl_444 (Tb3(4)) | 2 | −12.722 | 29.742 | 0 | −12.202 | 0.007 | 0.52 |
C_rbl_348 (Tb3(2)) | 2 | −17.995 | 16.156 | 0 | −6.523 | 0.003 | −6.921 |
Ada−C−rbl_276(Tb3(1)) | 2 | −14.584 | 37.724 | 0 | −24.685 | 0 | −24.438 |
Env_264 (Tb3(3)) | 2 | 3.158 | 29.921 | 0 | −11.775 | 0 | −12.728 |
Molecule | CNS | Human Oral Absorption | Rule of Five Violation | Rule of Three Violation |
---|---|---|---|---|
Nanotube (5,5) | 1 | 1 | 2 | 1 |
Nanotube (3,3) | 1 | 1 | 2 | 1 |
C70 | 1 | 1 | 2 | 1 |
C60 | 1 | 1 | 2 | 1 |
C_rbl_456 (Tb3(5) | −2 | 1 | 3 | 2 |
C_rbl_444 (Tb3(4)) | −2 | 1 | 3 | 2 |
C_rbl_348 (Tb3(2)) | −2 | 1 | 3 | 2 |
Ada−C−rbl _276 (Tb3(1)) | −2 | 1 | 3 | 2 |
Env_264 (Tb3(3)) | −2 | 1 | 3 | 2 |
Structure | Frequency (%) | Structure | Frequency (%) |
---|---|---|---|
M = 31.295 | 1.212 | M = 30.820 | 1.212 |
M = 29.809 | 1.212 | M = 251.659 | 3.773 |
M = 31.034 | 4.692 | M = 30.612 | 8.493 |
M = 10.646 | 2.877 | M =14.352 | 4.721 |
M =10.492 | 14.352 | M =14.358 | 6.556 |
M =256.254 | M = 284.22 | M = 224.256 |
M = 198.306 | M = 246.303 | M = 230.304 |
M = 214.305 | M = 262.302 | M = 278.301 |
M = 376.446 | M = 312.45 | M = 294.3 |
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Diudea, M.V.; Lungu, C.N.; Nagy, C.L. Cube-Rhombellane Related Structures: A Drug Perspective. Molecules 2018, 23, 2533. https://doi.org/10.3390/molecules23102533
Diudea MV, Lungu CN, Nagy CL. Cube-Rhombellane Related Structures: A Drug Perspective. Molecules. 2018; 23(10):2533. https://doi.org/10.3390/molecules23102533
Chicago/Turabian StyleDiudea, Mircea Vasile, Claudiu Nicolae Lungu, and Csaba Levente Nagy. 2018. "Cube-Rhombellane Related Structures: A Drug Perspective" Molecules 23, no. 10: 2533. https://doi.org/10.3390/molecules23102533