Incorporation of a Nitric Oxide Donating Motif into Novel PC-PLC Inhibitors Provides Enhanced Anti-Proliferative Activity
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis of N-Nitrosylated Benzylamines
2.2. Assessment of NO Donor Activity by N-Nitrosylated Benzylamines
2.3. Anti-Proliferative Activity of N-Nitrosylated Benzylamines
3. Materials and Methods
3.1. Synthesis of N-Nitrosylated Derivatives
3.1.1. Synthesis of Compounds 2–6a–m
3.1.2. General Procedure for Synthesis of N-Nitrosylated Benzylamines 7a–m
3.2. Nitric Oxide Release Assay
3.2.1. Cell Culture
3.2.2. Intracellular NO Release and Detection
3.3. Cell Proliferation Assay
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Benzylic Substitution | Relative 3H Thymidine Incorporation (% ± s.e.m) at 10 µM in MDA-MB-231 Cells | |
---|---|---|
Benzylamines 6 [23] | N-Nitrosylated Benzylamines 7 | |
H (a) | 89.1 ± 1.9 | 59.0 ± 4.4 ** |
2-F (b) | 105.9 ± 0.1 | 51.4 ± 1.7 *** |
3-F (c) | 85.9 ± 1.6 | 42.1 ± 4.2 *** |
4-F (d) | 81.4 ± 0.8 | 44.1 ± 3.0 *** |
2-Cl (e) | 77.1 ± 5.4 | 30.8 ± 0.5 ** |
3-Cl (f) | 79.4 ± 2.7 | 33.9 ± 0.1 *** |
4-Cl (g) | 77.1 ± 0.9 | 27.0 ± 0.7 *** |
2-Br (h) | 66.6 ± 3.4 | 4.1 ± 0.0 *** |
3-Br (i) | 87.4 ± 8.4 | 24.5 ± 0.7 ** |
4-Br (j) | 77.0 ± 2.3 | 18.8 ± 1.9 *** |
2-OMe (k) | 88.0 ± 5.3 | 41.6 ± 1.6 ** |
3-OMe (l) | 95.7 ± 11.0 | 71.7 ± 2.5 |
4-OMe (m) | 103.0 ± 8.0 | 25.2 ± 1.5 *** |
D609 | 99.00 ± 2.1 | |
Positive Control | 100 ± 0.9 |
Benzylic Substitution | Relative 3H Thymidine Incorporation (% ± s.e.m) at 10 µM in HCT-116 Cells | |
---|---|---|
Benzylamines 6 [23] | N-Nitrosylated Benzylamines 7 | |
H (a) | 101.3 ± 0.5 | 75.5 ± 3.4 ** |
2-F (b) | 101.1 ± 0.3 | 75.7 ± 0.4 *** |
3-F (c) | 91.0 ± 4.3 | 63.2 ± 11.3 |
4-F (d) | 89.6 ± 5.5 | 61.0 ± 3.9 * |
2-Cl (e) | 86.5 ± 1.0 | 39.7 ± 1.9 *** |
3-Cl (f) | 92.1 ± 0.1 | 50.1 ± 2.4 *** |
4-Cl (g) | 83.7 ± 1.2 | 39.5 ± 2.7 *** |
2-Br (h) | 92.0 ± 0.4 | 24.8 ± 4.4 *** |
3-Br (i) | 95.1 ± 1.8 | 46.4 ± 3.5 *** |
4-Br (j) | 88.8 ± 0.1 | 41.3 ± 3.2 *** |
2-OMe (k) | 96.3 ± 0.4 | 64.9 ± 9.9 * |
3-OMe (l) | 102.6 ± 0.4 | 84.7 ± 5.0 * |
4-OMe (m) | 100.2 ± 0.3 | 50.4 ± 7.8 * |
D609 | 98.40 ± 3.2 | |
Positive Control | 100 ± 2.4 |
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Rees, S.W.P.; Rees, T.A.; Leung, E.; Walker, C.S.; Barker, D.; Pilkington, L.I. Incorporation of a Nitric Oxide Donating Motif into Novel PC-PLC Inhibitors Provides Enhanced Anti-Proliferative Activity. Int. J. Mol. Sci. 2021, 22, 11518. https://doi.org/10.3390/ijms222111518
Rees SWP, Rees TA, Leung E, Walker CS, Barker D, Pilkington LI. Incorporation of a Nitric Oxide Donating Motif into Novel PC-PLC Inhibitors Provides Enhanced Anti-Proliferative Activity. International Journal of Molecular Sciences. 2021; 22(21):11518. https://doi.org/10.3390/ijms222111518
Chicago/Turabian StyleRees, Shaun W. P., Tayla A. Rees, Euphemia Leung, Christopher S. Walker, David Barker, and Lisa I. Pilkington. 2021. "Incorporation of a Nitric Oxide Donating Motif into Novel PC-PLC Inhibitors Provides Enhanced Anti-Proliferative Activity" International Journal of Molecular Sciences 22, no. 21: 11518. https://doi.org/10.3390/ijms222111518