QSAR Study of Antimicrobial 3-Hydroxypyridine-4-one and 3-Hydroxypyran-4-one Derivatives Using Different Chemometric Tools
Abstract
:1. Introduction
2. Experimental Section
2.1. Software
2.2. Data set and descriptor generation
2.3. Data screening and model building
3. Results and Discussion
3.1. GA-PLS
3.2. FA-MLR and PCRA
4. Conclusions
Acknowledgments
References and notes
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Compound | X | R2 | R3 | R5 | R6 |
---|---|---|---|---|---|
1 | NH | CH3 | OH | CH2-Ra | H |
2 | NH | C2H5 | OH | CH2-Ra | H |
3 | NH | CH3 | OH | CH2-N(CH3)2 | H |
4 | NH | C2H5 | OH | CH2-N(CH3)2 | H |
5 | NH | CH3 | OH | CH2-N(C2H5)2 | H |
6 | NH | C2H5 | OH | CH2-N(C2H5)2 | H |
7 | N-Ph | CH3 | OH | H | H |
8 | N-m-OH-Ph | CH3 | OH | H | H |
9 | N-C3H7 | CH3 | OH | H | H |
10 | N-C4H9 | CH3 | OH | H | H |
11 | O | CH2Cl | H | OH | H |
12 | O | CH3 | H | OH | H |
13 | O | CH2OH | OH | H | CH3 |
14 | O | CH2OH | OCH2Ph | H | CH3 |
15 | O | CHO | OCH2Ph | H | CH3 |
16 | O | COOH | OCH2Ph | H | CH3 |
17 | O | CONHRb | OCH2Ph | H | CH3 |
18 | O | CONHRc | OCH2Ph | H | CH3 |
19 | O | CONHRd | OCH2Ph | H | CH3 |
20 | O | CONHRb | OH | H | CH3 |
21 | O | CONHRc | OH | H | CH3 |
22 | O | CONHRd | OH | H | CH3 |
23 | O | CH2OH | H | OCH2Ph | H |
24 | O | COOH | H | OCH2Ph | H |
25 | O | CONHPh | H | OCH2Ph | H |
26 | N-CH3 | CONHPh | H | OCH2Ph | H |
27 | N-CH3 | CONHPh | H | OH | H |
28 | O | CONH-Re | H | OCH2Ph | H |
29 | N-CH3 | CONH-Re | H | OCH2Ph | H |
30 | N-CH3 | CONH-Re | H | OH | H |
31 | O | CH2OH | H | OH | H |
Descriptor Type | Molecular Description |
---|---|
Constitutional | Mean atomic van der Waals volume (Mv) (scaled on Carbon atom), no. of heteroatoms, no. of multiple bonds (nBM), no. of rings, no. of circuits, no of H-bond donors, no of H-bond acceptors, no. of Nitrogen atoms (nN), chemical composition, sum of Kier-Hall electrotopological states (Ss), mean atomic polarizability (Mp), number of rotable bonds (RBN), mean atomic Sanderson electronegativity (Me), etc.
|
Topological | Narumi harmonic topological index (HNar), Total structure connectivity index (Xt), information content index (IC), mean information content on the distance degree equality (IDDE), total walk count, path/walk-Randic shape indices (PW3, PW4, PW5, Zagreb indices, Schultz indices, Balaban J index (such as MSD) Wiener indices, Information content index (neighborhood symmetry of 2-order) (IC2), Ratio of multiple path count to path counts (PCR), Lovasz-Pelikan index (leading eigenvalue) (LP1), total information content index (neighborhood symmetry of 1-order) (TIC1), reciprocal hyper-detour index (Rww), Average connectivity index chi-5 (X5A), piID (conventional bond-order ID number), etc.
|
Geometrical | 3D Petijean shape index (PJI3), Asphericity (ASP), Gravitational index, Balaban index, Wiener index, Length-to-breadth ratio by WHIM (L/Bw), etc.
|
Quantum | Highest occupied Molecular Orbital Energy (HOMO), Lowest Unoccupied Molecular Orbital Energy (LUMO), Most positive charge (MPC), Sum of square of positive charges (SSPC), Sum of square of negative charges (SSNC), Sum of positive charges (SUMPC), Sum of negative charges (SUMNC), Sum of absolute of charges (SAC), Standard deviation (Std), Total dipole moment (DMt), Molecular dipole moment at X-direction (DMX), Molecular dipole moment at Y-direction (DMY), Molecular dipole moment at Z-direction (DMZ), Electronegativity (χ= −0.5 (HOMO-LUMO)), Electrophilicity (ω= χ2/2 η), Hardness (η = 0.5 (HOMO+LUMO)), Softness (S=1/ η).
|
Functional group | Number of total secondary C(sp3) (nCs), Number of total tertiary carbons (nCt), Number of H-bond acceptor atoms (nHAcc), Number of secondary amides (aliphatic) (nCONHR), Number of unsubstituted aromatic C (nCaH), Number of ethers (aromatic) (nRORPh), Number of ketones (aliphatic) (nCO), Number of tertiary amines (aliphatic) (nNR2), Number of phenols (nOHPh), Number of total primary C(sp3) (nCp), etc.
|
Chemical | LogP (Octanol-water partition coefficient), Hydration Energy (HE), Polarizability (Pol), Molar refractivity (MR), Molecular volume (V), Molecular surface area (SA).
|
Compound | Experimental pMICa | Predicted pMIC | REP b (%) |
---|---|---|---|
1 | 3.29 | 3.3205 | 0.9173 |
2 | 3.29 | 3.3007 | 0.3242 |
3 | 3.29 | 3.2266 | −1.9664 |
4* | 3.29 | 3.3976 | 3.1675 |
5 | 4.19 | 3.7498 | −11.740 |
6 | 3.29 | 3.3205 | 0.9173 |
7 | 3.89 | 3.8255 | −1.6850 |
8 | 3.29 | 3.2698 | −0.6172 |
9 | 3.29 | 3.2886 | −0.0440 |
10* | 3.89 | 3.9283 | 0.9738 |
11 | 3.59 | 3.6207 | 0.8470 |
12 | 3.59 | 3.7254 | 3.6340 |
13 | 3.59 | 3.5063 | −2.3883 |
14 | 3.59 | 3.6212 | 0.8627 |
15* | 4.19 | 4.1563 | −0.8119 |
16 | 3.59 | 3.5611 | −0.8123 |
17 | 3.59 | 3.6177 | 0.7647 |
18 | 3.59 | 3.5548 | −0.9915 |
19* | 3.89 | 3.8950 | 0.1293 |
20 | 4.19 | 4.0995 | −2.2079 |
21 | 3.59 | 3.7117 | 3.2787 |
22 | 5.10 | 5.0840 | −0.3141 |
23 | 3.59 | 3.5533 | −1.0318 |
24* | 3.59 | 3.7223 | 3.5534 |
25 | 3.89 | 3.9222 | 0.8214 |
26 | 3.89 | 3.9779 | 2.2092 |
27 | 4.80 | 4.8022 | 0.0453 |
28 | 3.89 | 3.8591 | −0.8011 |
29 | 3.59 | 3.4907 | −2.8470 |
30* | 4.49 | 4.5105 | 0.4549 |
31 | 3.59 | 3.4728 | −3.3746 |
Compd. | Experimental pMIC | Predicted pMIC | REP(%) |
---|---|---|---|
2 | 3.29 | 3.4139 | 3.6304 |
4* | 3.29 | 3.3893 | 2.9303 |
5 | 3.89 | 3.8920 | 0.0514 |
6 | 3.29 | 3.3591 | 2.0577 |
7 | 3.29 | 3.3835 | 2.7631 |
8 | 3.59 | 3.6477 | 1.5813 |
9 | 3.29 | 3.3208 | 0.9272 |
10* | 3.59 | 3.6196 | 0.8175 |
11 | 3.89 | 3.9567 | 1.6857 |
12 | 3.89 | 3.7481 | −3.7870 |
13 | 3.89 | 3.9092 | 0.4922 |
14 | 3.89 | 3.7076 | −4.9191 |
15 | 3.89 | 3.8892 | −0.0203 |
16 | 3.89 | 3.8422 | −1.2433 |
17* | 4.49 | 4.3961 | −2.1360 |
18 | 4.49 | 4.4476 | −0.9524 |
19 | 3.89 | 3.7076 | −4.9191 |
20 | 3.89 | 3.8014 | −2.3296 |
21 | 3.89 | 3.9525 | 1.5813 |
23 | 3.89 | 3.7450 | −3.8727 |
24* | 3.89 | 3.9056 | 0.3994 |
25 | 3.89 | 3.9969 | 2.6755 |
26 | 3.89 | 3.8489 | −1.0691 |
27 | 3.89 | 3.7573 | −3.5304 |
28 | 3.89 | 3.9503 | 1.5262 |
29* | 3.89 | 3.9964 | 2.6619 |
30 | 3.89 | 3.8978 | 0.2006 |
31 | 3.89 | 3.8732 | −0.4333 |
1 | 2 | 3 | 4 | Commonality | |
---|---|---|---|---|---|
MPC | 0.588 | −0.105 | 0.587 | −0.313 | 0.799 |
DMy | 0.195 | −0.054 | 0.762 | 0.071 | 0.627 |
HOMO | 0.059 | 0.637 | −0.013 | 0.620 | 0.794 |
Electonegativity | −0.643 | −0.206 | −0.199 | −0.496 | 0.741 |
Mv | 0.751 | −0.413 | 0.362 | −0.259 | 0.934 |
Me | 0.001 | −0.781 | 0.097 | −0.298 | 0.708 |
RBN | 0.087 | 0.902 | 0.068 | 0.003 | 0.826 |
HNar | 0.866 | 0.051 | 0.217 | −0.252 | 0.863 |
Xt | −0.645 | −0.505 | −0.307 | 0.081 | 0.772 |
IDDE | 0.746 | 0.359 | 0.215 | 0.324 | 0.837 |
LP1 | 0.667 | 0.460 | 0.368 | 0.292 | 0.877 |
TIC1 | 0.714 | 0.413 | 0.175 | 0.127 | 0.726 |
PJI3 | 0.375 | 0.611 | −0.315 | −0.276 | 0.689 |
nCS | −0.559 | 0.578 | −0.411 | 0.199 | 0.855 |
nCaH | 0.894 | −0.140 | −0.143 | −0.079 | 0.845 |
nCONHR | 0.261 | 0.220 | 0.695 | −0.906 | 0.765 |
nCO | −0.082 | 0.081 | −0.214 | 0.853 | 0.787 |
pMIC S. aureus | 0.041 | −0.116 | 0.898 | −0.051 | 0.824 |
%variance | 29.87 | 20.10 | 17.15 | 12.12 | 79.24 |
1 | 2 | 3 | 4 | 5 | Commonality | |
---|---|---|---|---|---|---|
Std | −0.491 | −0.431 | −0.459 | −0.107 | 0.095 | 0.657 |
DMz | −0.007 | 0.102 | −0.209 | 0.860 | 0.322 | 0.898 |
HOMO | 0.240 | 0.811 | −0.156 | −0.349 | 0.014 | 0.861 |
Electonegativity | −0.706 | −0.389 | 0.142 | 0.323 | −0.310 | 0.871 |
X5A | −0.627 | −0.664 | −0.134 | −0.102 | 0.129 | 0.879 |
PW3 | −0.166 | 0.594 | −0.377 | −0.158 | 0.893 | 0.584 |
PW5 | 0.913 | −0.079 | 0.055 | 0.135 | −0.132 | 0.879 |
IC2 | 0.579 | 0.272 | −0.164 | 0.210 | 0.584 | 0.820 |
piID | 0.750 | −0.070 | −0.333 | −0.190 | −0.208 | 0.758 |
ASP | −0.075 | 0.087 | 0.866 | −0.198 | 0.322 | 0.905 |
L/Bw | 0.064 | 0.117 | 0.926 | −0.023 | 0.164 | 0.902 |
nCp | −0.206 | 0.754 | −0.224 | −0.097 | −0.325 | 0.777 |
nNR2 | −0.366 | 0.722 | 0.148 | 0.287 | −0.234 | 0.814 |
nOHPh | −0.191 | −0.415 | −0.165 | −0.447 | 0.356 | 0.562 |
nRORPh | 0.571 | −0.522 | 0.379 | 0.002 | −0.341 | 0.858 |
pMIC C. albicans | 0.628 | −0.627 | −0.277 | −0.107 | 0.602 | 0.872 |
%variance | 22.58 | 20.58 | 14.71 | 14.02 | 8.71 | 80.60 |
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Sabet, R.; Fassihi, A. QSAR Study of Antimicrobial 3-Hydroxypyridine-4-one and 3-Hydroxypyran-4-one Derivatives Using Different Chemometric Tools. Int. J. Mol. Sci. 2008, 9, 2407-2423. https://doi.org/10.3390/ijms9122407
Sabet R, Fassihi A. QSAR Study of Antimicrobial 3-Hydroxypyridine-4-one and 3-Hydroxypyran-4-one Derivatives Using Different Chemometric Tools. International Journal of Molecular Sciences. 2008; 9(12):2407-2423. https://doi.org/10.3390/ijms9122407
Chicago/Turabian StyleSabet, Razieh, and Afshin Fassihi. 2008. "QSAR Study of Antimicrobial 3-Hydroxypyridine-4-one and 3-Hydroxypyran-4-one Derivatives Using Different Chemometric Tools" International Journal of Molecular Sciences 9, no. 12: 2407-2423. https://doi.org/10.3390/ijms9122407
APA StyleSabet, R., & Fassihi, A. (2008). QSAR Study of Antimicrobial 3-Hydroxypyridine-4-one and 3-Hydroxypyran-4-one Derivatives Using Different Chemometric Tools. International Journal of Molecular Sciences, 9(12), 2407-2423. https://doi.org/10.3390/ijms9122407