Molecular Topology for the Discovery of New Broad-Spectrum Antibacterial Drugs
"> Figure 1
<p>DF1 pharmacological distribution diagram. Black bars: Training Inactives. White bars: Training Actives. Dashed line: Test Inactives. Straight line: Test Actives.</p> "> Figure 2
<p>DF2 pharmacological distribution diagram. Black bars: Training Inactives. White bars: Training Actives. Dashed line: Test Inactives. Straight line: Test Actives.</p> "> Figure 3
<p>DF3 pharmacological distribution diagram. Black bars: Training Inactives. White bars: Training Actives. Dashed line: Test Inactives. Straight line: Test Actives.</p> "> Figure 4
<p>DF4 pharmacological distribution diagram. Black bars: Training Inactives. White bars: Training Actives. Dashed line: Test Inactives. Straight line: Test Actives.</p> ">
Abstract
:1. Introduction
2. Materials and Methods
2.1. Compound Selection
2.2. Topological Descriptors
2.3. Linear Discriminant Analysis (LDA)
2.4. Pharmacological Distribution Diagrams
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Group | Active | Inactive | % Success |
---|---|---|---|
Training active | 35 | 3 | 92.1 |
Training inactive | 5 | 33 | 86.8 |
Test active | 11 | 1 | 91.7 |
Test inactive | 2 | 9 | 81.8 |
JK Training active | 35 | 3 | 92.1 |
JK Training inactive | 5 | 33 | 86.8 |
Group | Active | Inactive | % Success |
---|---|---|---|
Training active | 37 | 1 | 97.4 |
Training inactive | 3 | 35 | 92.1 |
Test active | 11 | 1 | 91.7 |
Test inactive | 0 | 11 | 100 |
JK Training active | 35 | 3 | 92.1 |
JK Training inactive | 6 | 32 | 84.2 |
Active | Inactive | % Success | |
---|---|---|---|
Training active | 36 | 2 | 94.7 |
Training inactive | 3 | 35 | 92.1 |
Test active | 11 | 1 | 91.7 |
Test inactive | 0 | 11 | 100 |
JK Training active | 35 | 3 | 92.1 |
JK Training inactive | 4 | 34 | 89.5 |
Group | Active | Inactive | % Success |
---|---|---|---|
Training active | 37 | 1 | 97.4 |
Training inactive | 4 | 34 | 89.5 |
Test active | 12 | 0 | 100 |
Test inactive | 0 | 11 | 100 |
JK Training active | 36 | 2 | 94.7 |
JK Training inactive | 4 | 34 | 89.5 |
Compound | DF1 1 | ClasDF1 2 | DF2 1 | ClasDF2 2 | DF3 1 | ClasDF3 2 | DF4 1 | ClasDF4 2 |
---|---|---|---|---|---|---|---|---|
ABT-492 | 4.950 | + | 3.886 | + | 8.906 | + | 6.043 | + |
Amifloxacin | 1.018 | − | 0.473 | + | 3.797 | + | 6.610 | + |
BAYy3118 | 1.899 | − | 4.249 | + | 4.345 | + | 8.537 | + |
BMS-340278 | −1.084 | − | 2.272 | + | 0.571 | + | 3.836 | + |
BMS-340280 | 4.423 | + | 6.162 | + | 7.714 | + | 6.312 | + |
CFC-222 | 4.369 | + | 4.355 | + | 8.364 | + | 8.289 | + |
Clinafloxacin | 3.267 | + | 4.516 | + | −1.173 | − | 2.194 | + |
CS-940 | 6.137 | + | 6.079 | + | 8.585 | + | 7.711 | + |
Difloxacin | 0.888 | − | 1.030 | + | 3.058 | + | 3.148 | + |
DQ-113 | 7.031 | + | 8.656 | + | 8.852 | + | 8.107 | + |
DW-116 | 1.281 | − | 1.345 | + | 3.365 | + | 3.254 | + |
DW286 | 5.321 | + | 1.942 | + | 1.597 | + | 3.437 | + |
DX-619 | 3.772 | + | 6.674 | + | 2.660 | + | 3.626 | + |
E-4441 | 8.088 | + | 5.189 | + | 9.835 | + | 9.477 | + |
E-4474 | 6.675 | + | 5.696 | + | 3.666 | + | 5.164 | + |
E-4501 | 4.482 | + | 5.557 | + | 6.532 | + | 8.911 | + |
E-4534 | 6.646 | + | 5.690 | + | 4.779 | + | 6.532 | + |
E-4535 | 3.968 | + | 4.026 | + | 1.812 | + | 4.165 | + |
E-4767 | 3.762 | + | 4.552 | + | 4.063 | + | 6.507 | + |
E-5065 | 4.155 | + | 4.417 | + | 3.292 | + | 6.326 | + |
Sparfloxacin | 5.597 | + | 6.220 | + | 11.507 | + | 12.839 | − |
Fleroxacin | 6.536 | + | 2.914 | + | 5.178 | + | 7.890 | + |
Garenoxacin | 3.172 | + | 4.498 | + | 4.661 | + | 4.229 | + |
Gatifloxacin | 2.807 | + | 4.236 | + | 5.433 | + | 8.125 | + |
Gemifloxacin | 0.941 | − | 2.268 | + | −1.575 | − | 0.198 | + |
Levofloxacin | 0.778 | − | 0.176 | + | 2.779 | + | 5.358 | + |
Lomefloxacin | 3.536 | + | 1.699 | + | 6.580 | + | 8.713 | + |
Norfloxacin | 0.835 | − | 0.040 | + | 1.270 | + | 3.048 | + |
Olamufloxacin | 6.884 | + | 8.159 | + | 7.029 | + | 7.670 | + |
Pazufloxacin | 3.439 | + | 3.256 | + | 3.095 | + | 5.559 | + |
Pefloxacin | 0.434 | − | 0.003 | + | 0.251 | + | 3.216 | + |
PGE-4175997 | −0.023 | − | 2.379 | + | 3.933 | + | 2.834 | + |
PGE-9509924 | 2.682 | + | 2.674 | + | −1.660 | − | 1.498 | + |
Sitafloxacin | 8.074 | + | 8.583 | + | 9.195 | + | 9.874 | + |
Temafloxacin | 2.727 | + | 2.363 | + | 9.035 | + | 7.899 | + |
Tosufloxacin | 4.105 | + | 2.931 | + | 1.552 | + | −0.242 | − |
Ulifloxacin | 2.050 | + | −1.955 | − | 2.920 | + | 8.097 | + |
WIN57273 | −0.958 | − | 4.073 | + | 1.545 | + | 1.421 | + |
Compound | DF1 | ClasDF1 | DF2 | ClasDF2 | DF3 | ClasDF3 | DF4 | ClasDF4 |
---|---|---|---|---|---|---|---|---|
Cinchophen | 0.043 | − | −1.933 | − | −6.168 | − | −6.935 | − |
Ferron | −3.755 | − | −7.099 | − | −7.320 | − | −6.572 | − |
Inact2 | −4.096 | − | 3.663 | + | 1.145 | + | 1.959 | + |
Inact3 | −4.735 | − | −2.664 | − | −8.127 | − | −6.905 | − |
Inact6 | −8.868 | − | −5.489 | − | −9.444 | − | −8.121 | − |
Inact7 | −7.901 | − | −5.529 | − | −10.331 | − | −6.187 | − |
Inact8 | −1.658 | − | −0.025 | − | −7.277 | − | −2.580 | − |
Inact9 | 1.536 | − | −0.030 | − | −2.731 | − | 3.266 | + |
Inact10 | −1.076 | − | −1.284 | − | −7.940 | − | −2.100 | − |
Inact11 | −1.201 | − | −0.817 | − | 1.713 | + | 2.628 | + |
Inact12 | −0.806 | − | 2.448 | + | −0.090 | − | 2.777 | + |
Inact14 | −1.317 | − | −3.994 | − | −8.495 | − | −6.188 | − |
Inact15 | −1.072 | − | −3.560 | − | −8.141 | − | −6.040 | − |
Inact17 | −2.475 | − | −3.917 | − | −8.041 | − | −6.189 | − |
Inact18 | −2.222 | − | −3.484 | − | −7.687 | − | −6.032 | − |
Inact19 | −2.319 | − | −0.060 | − | −7.177 | − | −5.624 | − |
Inact21 | −2.536 | − | −3.437 | − | −7.553 | − | −5.967 | − |
Inact22 | −3.930 | − | −8.739 | − | −10.208 | − | −8.742 | − |
Inact23 | −5.856 | − | −8.647 | − | −9.672 | − | −8.708 | − |
Inact25 | −4.954 | − | −6.981 | − | −8.297 | − | −10.772 | − |
Inact26 | −3.143 | − | −5.409 | − | −9.426 | − | −6.349 | − |
Inact27 | −4.655 | − | −6.235 | − | −7.203 | − | −9.497 | − |
Inact28 | −8.319 | − | −7.957 | − | −0.419 | − | −3.301 | − |
Inact29 | −8.432 | − | −8.115 | − | −10.453 | − | −12.242 | − |
Inact30 | −5.561 | − | −6.046 | − | −10.914 | − | −12.054 | − |
Inact32 | −4.364 | − | −5.992 | − | −8.236 | − | −7.927 | − |
Inact33 | −2.073 | − | −5.849 | − | −8.780 | − | −8.566 | − |
Inact34 | −6.510 | − | −5.899 | − | −7.985 | − | −10.005 | − |
Inact35 | −5.313 | − | −4.601 | − | −3.576 | − | −4.415 | − |
Inact36 | −3.528 | − | −4.374 | − | −3.124 | − | −4.794 | − |
Inact38 | −6.565 | − | −4.384 | − | −5.731 | − | −7.688 | − |
Inact40 | −2.240 | − | −4.083 | − | −5.346 | − | −6.583 | − |
Inact41 | 0.090 | − | −1.918 | − | −9.637 | − | −6.723 | − |
Inact42 | 0.581 | − | 0.045 | + | −6.066 | − | −8.086 | − |
Naptalam | −2.753 | − | −2.341 | − | −4.794 | − | −4.237 | − |
PGE-5215205 | −2.817 | − | −1.264 | − | −6.422 | − | −4.291 | − |
PGE-6116542 | 0.086 | − | −2.572 | − | −6.091 | − | −3.275 | − |
Quinoline | −10.175 | − | −2.702 | − | −8.621 | − | −3.372 | − |
Actives | ||||||||
---|---|---|---|---|---|---|---|---|
Compound | DF1 | ClasDF1 | DF2 | ClasDF2 | DF3 | ClasDF3 | DF4 | ClasDF4 |
A-80556 | 4.249 | + | 2.493 | + | 3.802 | + | 2.921 | + |
Balofloxacin | 2.040 | + | 4.199 | + | 4.580 | + | 7.367 | + |
BMS-433366 | 0.976 | − | 2.655 | + | 1.483 | + | 4.431 | + |
Ciprofloxacin | 1.862 | − | 3.858 | + | 2.035 | + | 4.915 | + |
DK-507k | 9.830 | + | 8.442 | + | 7.892 | + | 8.832 | + |
DV-7751a | 5.352 | + | 0.246 | + | 5.891 | + | 7.227 | + |
Enoxacin | 0.457 | − | 0.472 | + | 1.589 | + | 2.373 | + |
Grepafloxacin | 4.281 | + | 4.561 | + | 6.196 | + | 8.839 | + |
Moxifloxacin | 3.323 | + | 4.106 | + | 3.061 | + | 6.959 | + |
PGE-9262932 | 2.160 | + | 2.632 | + | −3.541 | − | 0.423 | + |
Rufloxacin | −3.376 | − | −0.296 | − | 1.319 | + | 5.263 | + |
Trovafloxacin | 6.145 | + | 5.586 | + | 4.622 | + | 4.501 | + |
Inactives | ||||||||
Compound | DF1 | ClasDF1 | DF2 | ClasDF2 | DF3 | ClasDF3 | DF4 | ClasDF4 |
Inact1 | −6.386 | − | −1.796 | − | −7.553 | − | −9.707 | − |
Benzoxiquine | −5.051 | − | −3.857 | − | −10.207 | − | −10.066 | − |
Inact4 | 0.031 | − | −1.528 | − | −5.412 | − | −2.152 | − |
Inact5 | 0.447 | − | −1.528 | − | −5.772 | − | −2.118 | − |
Inact13 | −0.877 | − | −0.185 | − | −7.770 | − | −5.683 | − |
Inact16 | −2.019 | − | −0.107 | − | −7.313 | − | −5.692 | − |
Inact20 | −2.789 | − | −3.871 | − | −7.907 | − | −6.123 | − |
KB-5246 | −8.966 | − | −10.697 | − | −16.779 | − | −16.688 | − |
Inact31 | −4.297 | − | −5.964 | − | −7.199 | − | −8.047 | − |
Inact37 | −2.737 | − | −4.380 | − | −10.664 | − | −11.606 | − |
Inact39 | −5.397 | − | −4.451 | − | −1.457 | − | −3.554 | − |
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Bueso-Bordils, J.I.; Alemán-López, P.A.; Suay-García, B.; Martín-Algarra, R.; Duart, M.J.; Falcó, A.; Antón-Fos, G.M. Molecular Topology for the Discovery of New Broad-Spectrum Antibacterial Drugs. Biomolecules 2020, 10, 1343. https://doi.org/10.3390/biom10091343
Bueso-Bordils JI, Alemán-López PA, Suay-García B, Martín-Algarra R, Duart MJ, Falcó A, Antón-Fos GM. Molecular Topology for the Discovery of New Broad-Spectrum Antibacterial Drugs. Biomolecules. 2020; 10(9):1343. https://doi.org/10.3390/biom10091343
Chicago/Turabian StyleBueso-Bordils, Jose I., Pedro A. Alemán-López, Beatriz Suay-García, Rafael Martín-Algarra, Maria J. Duart, Antonio Falcó, and Gerardo M. Antón-Fos. 2020. "Molecular Topology for the Discovery of New Broad-Spectrum Antibacterial Drugs" Biomolecules 10, no. 9: 1343. https://doi.org/10.3390/biom10091343