Discovery of Novel 3,4-Dihydro-2(1H)-Quinolinone Sulfonamide Derivatives as New Tubulin Polymerization Inhibitors with Anti-Cancer Activity
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Biological Evaluation
2.2.1. In Vitro Anticancer Activity
2.2.2. Inhibition of Tubulin Polymerization of D13
2.3. Docking Analysis
3. Conclusions
4. Experimental Section
4.1. Chemistry General Methods
4.2. Procedure for the Synthesis of Compound B
4.3. General Synthesis Process of Compounds C1–C16
4.4. General Synthesis Process of Compounds D1–D16
4.4.1. N-benzyl-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-7-sulfonamide (D1)
4.4.2. N-(4-bromobenzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-7-sulfonamide (D2)
4.4.3. N-(4-fluorobenzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-6-sulfonamide (D3)
4.4.4. N-(4-chlorobenzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-6-sulfonamide (D4)
4.4.5. N-(4-methylbenzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-6-sulfonamide (D5)
4.4.6. N-(4-(dimethylamino)benzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-6-sulfonamide (D6)
4.4.7. N-(3-methylbenzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-6-sulfonamide (D7)
4.4.8. N-(2-fluorobenzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-6-sulfonamide (D8)
4.4.9. N-(2-chlorobenzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-6-sulfonamide (D9)
4.4.10. N-(3,4-dichlorobenzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-6-sulfonamide (D10)
4.4.11. N-(5-chloro-2-fluorobenzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-8-sulfonamide (D11)
4.4.12. N-(3-methoxybenzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-6-sulfonamide (D12)
4.4.13. N-(4-methoxybenzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-6-sulfonamide (D13)
4.4.14. N-(3,4-dimethoxybenzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-6-sulfonamide (D14)
4.4.15. O-(2,5-dimethoxybenzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-6-sulfonamide (D15)
4.4.16. 2-oxo-N-(3,4,5-trimethoxybenzyl)-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-6-sulfonamide (D16)
4.5. In Vitro Anticancer Experiment
4.6. In Vitro Tubulin Polymerization Assay
4.7. Molecular Modeling
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Compd. | R | (μM) IC50 b | ||||
---|---|---|---|---|---|---|
HeLa | A549 | HCT116 | HepG-2 | L02 | ||
D1 | -H | 13.46 ± 2.15 | 14.15 ±1.26 | 25.90 ± 0.98 | 9.87 ± 2.49 | 20.73 ± 3.12 |
D2 | 4-Br | 3.98 ± 0.25 | 4.19 ± 1.27 | 1.95 ± 0.77 | 7.53 ± 0.27 | 10.56 ± 1.26 |
D3 | 4-F | 7.54 ± 1.48 | 18.24 ± 4.11 | 3.87 ± 0.12 | 6.31 ± 1.21 | 5.31 ± 1.08 |
D4 | 4-Cl | 9.67 ± 2.1 | 8.49 ± 1.77 | 4.21 ± 0.5 | 4.12 ± 0.55 | 6.35 ± 2.03 |
D5 | 4-CH3 | 1.34 ± 0.3 | 2.96 ± 0.13 | 1.13 ± 0.01 | 2.36 ± 0.11 | 3.05 ± 0.19 |
D6 | 4-N(CH3)2 | 3.63 ± 0.98 | 2.42 ± 0.46 | 2.05 ± 0.11 | 4.74 ± 1.56 | 5.31 ± 1.02 |
D7 | 3-CH3 | 36.49 ± 3.59 | 34.99 ± 6.74 | 28.17 ± 4.26 | 44.31 ± 4.31 | 30.21 ± 2.56 |
D8 | 2-F | 21.62 ± 3.56 | >100 | 17.54 ± 1.33 | 50.91 ± 6.77 | 60.21 ± 4.21 |
D9 | 2-Cl | 16.94 ± 4.11 | 31.68 ± 4.55 | 12.16 ± 2.89 | 27.46 ± 3.28 | 36.25 ± 4.21 |
D10 | 3,4-Cl | 75.29 ± 10.32 | >100 | 51.24 ± 13.49 | - | 48.26 ± 6.64 |
D11 | 2-Cl-5-F | 38.41 ± 4.57 | 19.27 ± 2.38 | 25.48 ± 5.23 | 58.37 ± 6.93 | 65.31 ± 4.25 |
D12 | 3-OCH3 | 54.64 ± 8.15 | - | 48.23 ± 7.46 | 64.12 ± 7.56 | 56.26 ± 2.15 |
D13 | 4-OCH3 | 1.46 ± 0.11 | 1.57 ± 0.25 | 0.94 ± 0.31 | 1.82 ± 0.97 | 3.61 ± 1.02 |
D14 | 3,4-OCH3 | >100 | 49.28 ± 12.53 | 87.81 ± 15.23 | - | 66.52 ± 7.81 |
D15 | 2,5-OCH3 | 86.36 ± 14.23 | - | >100 | 75.36 ± 15.44 | >100 |
D16 | 3,4,5-OCH3 | 4.91 ± 0.76 | 7.34 ± 1.44 | 2.08 ± 0.24 | 5.48 ± 1.23 | 4.25 ± 0.87 |
5-Fu | - | 29.57 ± 3.21 | 8.71 ± 0.23 | 11.67 ± 2.37 | 18.31 ± 0.76 | 20.04 ± 1.25 |
CA-4 | - | 0.02 ± 0.001 | 0.12 ± 0.023 | 0.04 ± 0.016 | 0.05 ± 0.021 | 0.15 ± 0.05 |
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Ma, J.; Gong, G.-H. Discovery of Novel 3,4-Dihydro-2(1H)-Quinolinone Sulfonamide Derivatives as New Tubulin Polymerization Inhibitors with Anti-Cancer Activity. Molecules 2022, 27, 1537. https://doi.org/10.3390/molecules27051537
Ma J, Gong G-H. Discovery of Novel 3,4-Dihydro-2(1H)-Quinolinone Sulfonamide Derivatives as New Tubulin Polymerization Inhibitors with Anti-Cancer Activity. Molecules. 2022; 27(5):1537. https://doi.org/10.3390/molecules27051537
Chicago/Turabian StyleMa, Juan, and Guo-Hua Gong. 2022. "Discovery of Novel 3,4-Dihydro-2(1H)-Quinolinone Sulfonamide Derivatives as New Tubulin Polymerization Inhibitors with Anti-Cancer Activity" Molecules 27, no. 5: 1537. https://doi.org/10.3390/molecules27051537
APA StyleMa, J., & Gong, G.-H. (2022). Discovery of Novel 3,4-Dihydro-2(1H)-Quinolinone Sulfonamide Derivatives as New Tubulin Polymerization Inhibitors with Anti-Cancer Activity. Molecules, 27(5), 1537. https://doi.org/10.3390/molecules27051537