Molecular Docking and Fluorescence Characterization of Benzothieno[3,2-d]pyrimidin-4-one Sulphonamide Thio-Derivatives, a Novel Class of Selective Cyclooxygenase-2 Inhibitors
Abstract
:1. Introduction
- N-[2-[(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)thio]-4-oxo[1]benzothieno[3,2-d]pyrimidin-3(4H)yl]methanesulfonamide (1);
- N-[2-[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)thio]-4oxo[1]benzothieno [3,2-d]pyrimidin-3(4H)yl]methanesulfonamide (2);
- N-[2-[(2,4-nitrophenyl)thio]-4-oxo[1]benzothieno[3,2-d]pyrimidin-3(4H)yl]methanesulfonamide (4);
- N-[2-(cyclohexylthio)-4-oxo[1]benzothieno[3,2-d]pyrimidin-3(4H)yl]methanesulfonamide (8);
- N-[2-[(2,4-difluorophenyl)thio]-4-oxo[1]benzothieno[3,2-d]pyrimidin-(4H)yl]methane-sulfonamide (9);
- 2-({3-[(methylsulfonyl)amino]-4-oxo-3,4-dihydro[1]benzothieno[3,2-d]pyrimidin-2-yl}thio)benzoic acid (10).
Compounds | NCTC2544 | J774 | ||
---|---|---|---|---|
iNOS | COX-2 | iNOS | COX-2 | |
1 | 7.0 ± 0.2 | 6.8 ± 0.5 | 7.3 ± 0.3 | 6.9 ± 0.9 |
2 | 7.0 ± 0.9 | 6.7 ± 0.3 | 6.5 ± 0.5 | 6.9 ± 0.5 |
4 | 5.0 ± 0.2 | 4.5 ± 0.5 | 4.8 ± 0.3 | 5.0 ± 0.1 |
8 | 5.8 ± 0.3 | 6.1 ± 1.5 | 6.5 ± 0.9 | 6.2 ± 0.6 |
9 | 8.0 ± 0.3 | 8.0 ± 1.0 | 7.8 ± 0.9 | 8.2 ± 0.4 |
10 | 6.5 ± 1.3 | 6.2 ± 0.8 | 6.5 ± 1.5 | 6.2 ± 0.5 |
2. Results and Discussion
2.1. Docking Study
Compound | Docking energies (ΔG) (kcal/mol) | Number of H-bonds | Donor/Acceptor Hydrogen bond | H-bond distance (Å) |
---|---|---|---|---|
Naproxen | −9.0 | 2 | ARG-120:NH1 | 1.863 |
TYR-355:OH 1 | 2.165 | |||
Nimesulide | −7.3 | 2 | ARG-120:NH1 | 3.088 |
TYR-355:OH 1 | 2.737 | |||
Derivative 1 | −7.9 | 2 | ARG-120:NH1 | 3.149 |
TYR-112:OH 1 | 2.806 | |||
Derivative 2 | −8.1 | 2 | ARG-120:NH1 | 3.002 |
TYR-112:OH 1 | 2.788 | |||
Derivative 4 | −9.4 | 3 | ASN-382:NH2 | 2.867 |
HIS-386:NH2 | 2.945 | |||
THR-212:OH1 | 2.692 | |||
Derivative 8 | −8.9 | 1 | ARG-120:NH1 | 2.882 |
Derivative 9 | −9.1 | 2 | TYR-355:OH | 2.875 |
ARG-120:NH | 2.876 | |||
Derivative 10 | −8.2 | 2 | ARG-120:NH | 2.970 |
TYR-355:OH | 3.120 |
2.2. Spectroscopic Characterization
Derivative | ε (λmax) | ε (λmax) | Φfl |
---|---|---|---|
1 | 10,991 (340) | 9916 (354) | 0.080 |
2 | 8304 (338) | 7500 (352) | 0.013 |
4 | 9784 (338) | 8905 (352) | 0.032 |
8 | 9662 (338) | 8199 (350) | 0.055 |
9 | 10,773 (338) | 9855 (352) | 0.007 |
10 | 9435 (334) | 8643 (346) | 0.087 |
2.3. Fluorescence Microscopy
3. Experimental
3.1. General Information
3.2. Computational Method
3.3. Absorption and Emission Spectroscopy
3.4. Fluorescence Microscopy
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Barone, M.; Pannuzzo, G.; Santagati, A.; Catalfo, A.; De Guidi, G.; Cardile, V. Molecular Docking and Fluorescence Characterization of Benzothieno[3,2-d]pyrimidin-4-one Sulphonamide Thio-Derivatives, a Novel Class of Selective Cyclooxygenase-2 Inhibitors. Molecules 2014, 19, 6106-6122. https://doi.org/10.3390/molecules19056106
Barone M, Pannuzzo G, Santagati A, Catalfo A, De Guidi G, Cardile V. Molecular Docking and Fluorescence Characterization of Benzothieno[3,2-d]pyrimidin-4-one Sulphonamide Thio-Derivatives, a Novel Class of Selective Cyclooxygenase-2 Inhibitors. Molecules. 2014; 19(5):6106-6122. https://doi.org/10.3390/molecules19056106
Chicago/Turabian StyleBarone, Mariarita, Giovanna Pannuzzo, Andrea Santagati, Alfio Catalfo, Guido De Guidi, and Venera Cardile. 2014. "Molecular Docking and Fluorescence Characterization of Benzothieno[3,2-d]pyrimidin-4-one Sulphonamide Thio-Derivatives, a Novel Class of Selective Cyclooxygenase-2 Inhibitors" Molecules 19, no. 5: 6106-6122. https://doi.org/10.3390/molecules19056106