Self-Organizing Molecular Field Analysis on a New Series of COX-2 Selective Inhibitors: 1,5-Diarylimidazoles
Abstract
:1. Introduction
2. Computational Methods
2.1. Data sets and biological activities
2.2. Molecular modeling and docking
compda | R | -Log(IC50) | R | compda | -Log(IC50) |
---|---|---|---|---|---|
ZA1 | 4-F | 7.8539 | ZA16 | 4-OMe-2-F | 7.8239 |
ZA2 | 3-F | 7.1871 | ZA17 | 3,4-diCl | 8.2218 |
ZA3 | 2-F | 7.5528 | ZA18 | 4-OMe-3-F | 8.3979 |
ZA4 | H | 6.9101 | ZA19 | 4-Me-3-F | 8.2218 |
ZA5 | 4-Cl | 7.7447 | ZA20 | 4-OMe-3-Me | 7.8861 |
ZA6 | 4-Me | 7.7959 | ZA21 | 4-Me-3-OMe | 7.8239 |
ZA7 | 4-OMe | 7.9586 | ZA22 | 4-Cl-3-Me | 7.9586 |
ZA8 | 4-OEt | 8.3979 | ZA23 | 4-NMe-3-Cl | 7.5686 |
ZA9 | 4-Pr | 7.0000 | ZA24 | 4-OMe-3-Cl | 8.0969 |
ZA10 | 4-Pr' | 7.4089 | ZA25 | 4-OEt-3-Cl | 8.1549 |
ZA11 | 4-SMe | 6.9586 | ZA26 | 4-OEt-3-F | 7.602 |
ZA12 | 4-SEt | 7.2757 | ZA27 | 4-F-3-OMe | 7.7959 |
ZA13 | 4-NH2 | 6.7282 | ZA28 | 4-OMe-3,5-diCl | 8.1549 |
ZA14 | 4-NEt2 | 7.0969 | ZA29 | 3,5-diF | 7.1249 |
ZA15 | 2,4-diF | 8.1549 |
2.3. SOMFA 3D-QSAR models
Model No | Alignment | Charge | Resolution of grid (Å) |
---|---|---|---|
1 | a | AM1 | 0.5 |
2 | a | AM1 | 1 |
3 | a | MNDO | 0.5 |
4 | a | MNDO | 1 |
5 | a | PM3 | 0.5 |
6 | a | PM3 | 1 |
7 | b | AM1 | 0.5 |
8 | b | AM1 | 1 |
9 | b | MNDO | 0.5 |
10 | b | MNDO | 1 |
11 | b | PM3 | 0.5 |
12 | b | PM3 | 1 |
Model | c1 | r2 | s | F | rCV2 |
---|---|---|---|---|---|
1 | 0.685 | 0.478 | 0.351 | 24.711 | 0.455 |
2 | 0.679 | 0.464 | 0.356 | 23.342 | 0.439 |
3 | 0.765 | 0.458 | 0.358 | 22.858 | 0.434 |
4 | 0.752 | 0.446 | 0.361 | 21.736 | 0.421 |
5 | 0.633 | 0.503 | 0.342 | 27.316 | 0,473 |
6 | 0.658 | 0.479 | 0.351 | 24.835 | 0.451 |
7 | 0.500 | 0.525 | 0.335 | 29.820 | 0.486 |
8 | 0.514 | 0.532 | 0.333 | 30.680 | 0.500 |
9 | 0.512 | 0.546 | 0.327 | 32.515 | 0.507 |
10 | 0.506 | 0.544 | 0.328 | 32.149 | 0.500 |
11 | 0.644 | 0.498 | 0.344 | 26.826 | 0.458 |
12 | 0.645 | 0.497 | 0.344 | 26.716 | 0.464 |
Compd | Observed | Predicted | Residuala | Compd | Observed | Predicted | Residuala |
---|---|---|---|---|---|---|---|
1 | 7.85 | 7.46 | 0.40 | 12 | 7.28 | 7.43 | -0.16 |
2 | 7.19 | 7.57 | -0.38 | 13 | 6.73 | 7.42 | -0.70 |
3 | 7.55 | 7.70 | -0.15 | 14 | 7.10 | 7.12 | -0.02 |
4 | 6.91 | 7.11 | -0.20 | 15 | 8.15 | 7.94 | 0.21 |
5 | 7.75 | 8.00 | -0.25 | 16 | 7.82 | 7.70 | 0.13 |
6 | 7.80 | 7.57 | 0.23 | 17 | 8.22 | 7.79 | 0.43 |
7 | 7.96 | 7.69 | 0.27 | 18 | 8.40 | 8.15 | 0.25 |
8 | 8.40 | 7.76 | 0.64 | 19 | 8.22 | 8.21 | 0.01 |
9 | 7.00 | 7.18 | -0.18 | 20 | 7.89 | 7.73 | 0.16 |
10 | 7.41 | 7.32 | 0.09 | 21 | 7.82 | 7.58 | 0.24 |
11 | 6.96 | 7.41 | -0.45 | 22 | 7.96 | 8.02 | -0.06 |
Compd | Observed | Predicted | Residuala | Compd | Observed | Predicted | Residuala |
---|---|---|---|---|---|---|---|
1 | 7.59 | 8.02 | -0.43 | 5 | 7.80 | 7.92 | -0.13 |
2 | 8.10 | 8.11 | -0.01 | 6 | 8.15 | 7.66 | 0.50 |
3 | 8.15 | 7.82 | 0.34 | 7 | 7.13 | 7.66 | -0.53 |
4 | 7.60 | 7.83 | -0.23 |
3. Results and Discussion
4.Conclusion
Acknowledgements
References and notes
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Li, S.; Zheng, Y. Self-Organizing Molecular Field Analysis on a New Series of COX-2 Selective Inhibitors: 1,5-Diarylimidazoles. Int. J. Mol. Sci. 2006, 7, 220-229. https://doi.org/10.3390/i7070220
Li S, Zheng Y. Self-Organizing Molecular Field Analysis on a New Series of COX-2 Selective Inhibitors: 1,5-Diarylimidazoles. International Journal of Molecular Sciences. 2006; 7(7):220-229. https://doi.org/10.3390/i7070220
Chicago/Turabian StyleLi, Shunlai, and Yan Zheng. 2006. "Self-Organizing Molecular Field Analysis on a New Series of COX-2 Selective Inhibitors: 1,5-Diarylimidazoles" International Journal of Molecular Sciences 7, no. 7: 220-229. https://doi.org/10.3390/i7070220