Self-Assembled Alkylated Polyamine Analogs as Supramolecular Anticancer Agents
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis of Alkylated Analogs of PG11047
2.2. Self-Assembly
2.3. Inhibition of the Cancer Cell Growth and SMOX by the HPG Nanoparticles
3. Materials and Methods
3.1. Materials
3.2. General Procedure for the Synthesis and Characterization of (Z)-N1,N1′-(But-2-Ene-1,4-Diyl)Bis(N3-Ethylpropane-1,3-Diamine, (PG11047)
- Synthesis of (Z)-N1,N1′-(but-2-ene-1,4-diyl)bis(N3-propylpropane-1,3-diamine) (HPG-2): (yield—52%). 1H NMR (400 MHz, D2O): δ 5.99–5.98 (m, 2 H), 3.89–3.88 (m, 4 H), 3.23–3.15 (m, 8 H), 3.07–3.04 (m, 4 H), 2.19–2.11 (m, 4 H), 1.77–1.68 (m, 4 H), and 1.01–0.98 (t, J = 7.2 Hz, 6 H) ppm. 13C NMR (400 MHz, D2O): δ 126.35, 49.38, 44.22, 44.16, 44.11, 22.75, 19.13, and 10.11 ppm. MS (Orbitrap) calculated for C16H36N4, m/z 284.29, found 284.23 [M+].
- Synthesis of (Z)-N1,N1′-(but-2-ene-1,4-diyl)bis(N3-butylpropane-1,3-diamine) (HPG-3): (yield—50%). 1H NMR (400 MHz, D2O): δ 6.03–5.95 (m, 2 H), 3.89–3.88 (m, 4 H), 3.26–3.15 (m, 8 H), 3.11–3.04 (m, 4 H), 2.19–2.11 (m, 4 H), 1.72–1.65 (m, 4 H), 1.46–1.37 (m, 4 H), and 0.97–0.93 (t, J = 7.2 Hz, 6 H) ppm. 13C NMR (400 MHz, D2O): δ 126.35, 47.61, 44.23, 44.16, 44.11, 27.50, 22.76, 19.10, and 12.70 ppm. MS (Orbitrap) calculated for C18H40N4, m/z 312.32, found 313.25 [M + H]+.
- Synthesis of (Z)-N1,N1′-(but-2-ene-1,4-diyl)bis(N3-pentylpropane-1,3-diamine) (HPG-4): (yield—50%). 1H NMR (400 MHz, D2O): δ 6.00–5.98 (t, J = 4.4 Hz, 2 H), 3.89–3.80 (m, 4 H), 3.23–3.15 (m, 8 H), 3.11–3.07 (m, 4 H), 2.19–2.11 (m, 4 H), 1.75–1.67 (m, 4 H), 1.39–1.35 (m, 8 H), and 0.93–0.89 (m, 6 H) ppm. 13C NMR (400 MHz, D2O): δ 126.36, 47.85, 44.21, 44.17, 44.11, 27.78, 25.14, 22.75, 21.43, and 12.98 ppm. MS (Orbitrap) calculated for C20H44N4, m/z 340.35, found m/z 341.36 [M + H]+ and 171.18 [C10H23N2]+.
- Synthesis of (Z)-N1,N1′-(but-2-ene-1,4-diyl)bis(N3-hexylpropane-1,3-diamine) (HPG-5): (yield—53%). 1H NMR (400 MHz, D2O): δ 5.99–5.98 (m, 2 H), 3.89–3.88 (m, 4 H), 3.23–3.15 (m, 8 H), 3.10–3.07 (m, 4 H), 2.19–2.11 (m, 4 H), 1.74–1.67 (m, 4 H), 1.40–1.32 (m, 12 H), and 0.91–0.88 (m, 6 H). 13C NMR (400 MHz, D2O): δ 126.36, 47.88, 44.21, 44.17, 44.12, 30.40, 25.41, 25.30, 22.75, 21.68, and 13.18 ppm. MS (Orbitrap) calculated for C22H48N4, m/z 368.38, found m/z 369.39 [M + H]+ and 185.20 [C11H25N2]+.
- Synthesis of (Z)-N1,N1′-(but-2-ene-1,4-diyl)bis(N3-heptylpropane-1,3-diamine) (HPG-6): (yield—50%). 1H NMR (400 MHz, D2O): δ 5.99 (s, 2 H), 3.89–3.81 (m, 4 H), 3.23–3.15 (m, 8 H), 3.10–3.07 (m, 4 H), 2.19–2.11 (m, 4 H), 1.72–1.67 (m, 4 H), 1.37–1.31 (m, 16 H), and 0.90–0.87 (m, 6 H) ppm. 13C NMR (400 MHz, D2O): δ 126.36, 47.88, 44.21, 44.17, 44.12, 30.75, 27.83, 25.58, 25.46, 22.76, 21.86, and 13.30 ppm. MS (Orbitrap) calculated for C24H52N4, m/z 396.41, found m/z 397.43 [M + H]+ and 199.21 [C12H27N2]+.
- Synthesis of (Z)-N1,N1′-(but-2-ene-1,4-diyl)bis(N3-octylpropane-1,3-diamine) (HPG-7): (yield—51%). 1H NMR (400 MHz, D2O): δ 5.98–5.96 (t, J = 3.6 Hz, 2 H), 3.87–3.86 (m, 4 H), 3.21–3.13 (m, 8 H), 3.08–3.05 (m, 4 H), 2.16–2.09 (m, 4 H), 1.72–1.66 (m, 4 H), 1.39–1.28 (m, 20 H), and 0.88–0.85 (t, J = 5.6 Hz, 6 H) ppm. 13C NMR (400 MHz, D2O): δ 126.36, 47.88, 44.21, 44.17, 44.11, 30.97, 28.12, 28.10, 25.62, 25.45, 22.76, 21.95, and 13.35 ppm. MS (Orbitrap) calculated for C26H56N4, m/z 424.45, found m/z 425.45 [M + H]+ and 213.23 [C13H29N2]+.
- Synthesis of (Z)-N1,N1′-(but-2-ene-1,4-diyl)bis(N3-nonylpropane-1,3-diamine) (HPG-8): (yield—51%). 1H NMR (400 MHz, D2O): δ 5.98 (s, 2 H), 3.89–3.80 (m, 4 H), 3.23–3.15 (m, 8 H), 3.10–3.06 (m, 4 H), 2.18–2.11 (m, 4 H), 1.72–1.67 (m, 4 H), 1.36–1.30 (m, 24 H), and 0.88–0.87 (m, 6 H) ppm. 13C NMR (400 MHz, D2O): δ 126.36, 47.89, 44.21, 44.17, 44.11, 31.08, 28.40, 28.31, 28.14, 25.61, 25.46, 22.76, 22.00, and 13.38 ppm. MS (MALDI) calculated for C28H60N4, m/z 452.48, found 453.41 [M + H]+.
3.3. Measurement of Size and Zeta Potential of the Self-Assembled Nanoparticles
3.4. TEM Imaging
3.5. Cell Lines and Culture Conditions
3.6. SMOX Activity Assay and Enzyme Inhibition Studies
3.7. Cytotoxicity of the PG Analogs In Vitro
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
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Sample | Particle Size (nm) | PDI | Zeta Potential (mV) |
---|---|---|---|
HPG-2 | 173 ± 7 | 0.21 | 27 |
HPG-3 | 186 ± 3 | 0.064 | 24 |
HPG-4 | 174 ± 3 | 0.15 | 15 |
HPG-5 | 158 ± 4 | 0.23 | 16 |
HPG-6 | 225 ± 6 | 0.17 | 22 |
HPG-7 | 318 ± 8 | 0.13 | 11 |
HPG-8 | 626 ± 83 | 0.17 | 17 |
Sample Code | IC50 HCT116 | IC50 A549 | IC50 SMOX * |
---|---|---|---|
PG11047 | 8 µM | >10 µM | ND |
HPG-2 | <1.0 µM | <1.0 µM | ND |
HPG-3 | 8 µM | >10 µM | ND |
HPG-4 | >10 µM | 10 µM | ND |
HPG-5 | 8 µM | 7 µM | 90 µM |
HPG-6 | 3 µM | 3 µM | 30 µM |
HPG-7 | 1.0 µM | <1.0 µM | <10 µM |
HPG-8 | <1.0 µM | 7 µM | <10 µM |
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Sil, D.; Panja, S.; Jogdeo, C.M.; Kumar, R.; Yu, A.; Holbert, C.E.; Ding, L.; Foley, J.R.; Stewart, T.M.; Casero, R.A., Jr.; et al. Self-Assembled Alkylated Polyamine Analogs as Supramolecular Anticancer Agents. Molecules 2022, 27, 2441. https://doi.org/10.3390/molecules27082441
Sil D, Panja S, Jogdeo CM, Kumar R, Yu A, Holbert CE, Ding L, Foley JR, Stewart TM, Casero RA Jr., et al. Self-Assembled Alkylated Polyamine Analogs as Supramolecular Anticancer Agents. Molecules. 2022; 27(8):2441. https://doi.org/10.3390/molecules27082441
Chicago/Turabian StyleSil, Diptesh, Sudipta Panja, Chinmay M. Jogdeo, Raj Kumar, Ao Yu, Cassandra E. Holbert, Ling Ding, Jackson R. Foley, Tracy Murray Stewart, Robert A. Casero, Jr., and et al. 2022. "Self-Assembled Alkylated Polyamine Analogs as Supramolecular Anticancer Agents" Molecules 27, no. 8: 2441. https://doi.org/10.3390/molecules27082441