Dipeptides of S-Substituted Dehydrocysteine as Artzyme Building Blocks: Synthesis, Complexing Abilities and Antiproliferative Properties †
Abstract
:1. Introduction
2. Results and Discussion
2.1. Syntheses
2.2. Complexation of Cu2+ Ions by Compounds 9a and 10a
2.3. Antiproliferative Activity of Synthesized Compounds
3. Materials and Methods
3.1. General Procedure for Preparation of Dipeptides Containing S-Substituted Dehydrocysteine
3.2. General Procedure for Boc Deprotection
3.3. Potentiometric Titration
3.4. Spectroscopic Measurements (UV-Vis, CD, EPR)
3.5. Visualization of Complex Structures
3.6. Antiproliferative Activity Assessment
3.6.1. Cell Lines and Cultures Conditions
3.6.2. Antiproliferative Activity Assessment by Sulforhodamine B Assay
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compound No. | Name Abbreviation | Isolated Yield [%] |
---|---|---|
6a | Boc-Gly-ΔCys(S-triazole)-OMe | 93 |
7a | Boc-Phe-ΔCys(S-triazole)-OMe | 94 |
6b | Boc-Gly-ΔCys(S-4-phenylimidazole)-OMe | 93 |
7b | Boc-Phe-ΔCys(S-4-phenylimidazole)-OMe | 86 |
6c | Boc-Gly-ΔCys(S-5-methoxybenzoxazole)-OMe | 90 |
7c | Boc-Phe-ΔCys(S-5-methoxybenzoxazole)-OMe | 76 |
6d | Boc-Gly-ΔCys(S-benzothiazole)-OMe | 82 |
7d | Boc-Phe-ΔCys(S-benzothiazole)-OMe | 92 |
6e | Boc-Gly-ΔCys(S-adenine)-OMe | 61 |
7e | Boc-Phe-ΔCys(S-adenine)-OMe | 52 |
8 | Boc-Gly-ΔCys(S,S-bismethylbipyridine)-OMe | 80 |
9a | HCl Gly-ΔCys(S-triazole)-OMe | [a] |
10a | HCl Phe-ΔCys(S-triazole)-OMe | [a] |
9d | HCl Gly-ΔCys(S-benzothiazole)-OMe | [a] |
10d | HCl Phe-ΔCys(S-benzothiazole)-OMe | [a] |
9a | 10a | |||
---|---|---|---|---|
Form | logβ | logK | logβ | logK |
The protonation constants of free ligands | ||||
H3L | 25.31 ± 0.01 | 7.26 | 25.38 ± 0.02 | 6.85 |
H2L | 18.05 ± 0.01 | 7.96 (-NH2) | 18.53 ± 0.02 | 8.11 (-NH2) |
HL | 10.09 ± 0.01 | 10.09 | 10.42 ± 0.01 | 10.42 |
The stability constants of Cu(II)-complexes | ||||
CuLH2 | 23.52 ± 0.03 | 9.34 | 23.83 ± 0.03 | 8.83 |
CuL | 14.18 ± 0.01 | 10.42 | 15.00 ± 0.01 | 10.61 |
CuLH-1 | 3.76 ± 0.04 | - | 4.39 ± 0.03 | - |
Cu2L2H | 36.61 ± 0.03 | 14.45 | 37.54 ± 0.06 | 14.59 |
Cu2L2H-1 | 22.16 ± 0.06 | - | 22.95 ± 0.06 | - |
CuL2H2 | 36.46 ± 0.04 | 7.67 | - | - |
CuL2H | 28.79 ± 0.04 | 8.73 | 28.82 ± 0.11 | 8.45 |
CuL2 | 20.06 ± 0.04 | 11.35 | 20.37 ± 0.05 | - |
CuL2H-1 | 8.71 ± 0.07 | - | - | - |
Cpd. | MCF-7 | MDA-MB-231 | A-549 | LoVo | LoVoDX | Balb/3T3 |
---|---|---|---|---|---|---|
6b | 31.8 ± 7.8 | 35.0 ± 10.0 | 27.2 ± 7.7 | 32.4 ± 2.6 | [a] | 38.4 ± 3.5 |
6c | 5.3 ± 0.9 | 5.0 ± 0.8 | 6.2 ± 1.4 | 8.7 ± 1.1 | 6.4 ± 0.4 | 5.3 ± 1.2 |
6d | 4.5 ± 0.5 | 6.1 ± 0.6 | 5.6 ± 0.9 | 6.7 ± 0.7 | 6.2 ± 0.6 | 5.8 ± 0.9 |
7a | 74.5 ± 5.8 | 53.3 ± 5.5 | 60.7 ± 12.1 | 75.8 ± 6.5 | [a] | 19.7 ± 1.9 |
7b | 15.5 ± 2.5 | 15.2 ± 4.4 | 12.0 ± 4.0 | 16.4 ± 1.7 | 23.0 ± 2.2 | 7.6 ± 0.9 |
7c | 4.5 ± 0.4 | 7.1 ± 0.8 | 4.0 ± 1.1 | 6.3 ± 0.5 | 4.5 ± 0.4 | 5.3 ± 0.4 |
7d | 6.8 ± 0.5 | 10.8 ± 0.4 | 6.6 ± 1.4 | 9.6 ± 0.9 | 8.6 ± 0.9 | 3.1 ± 0.6 |
7e | 100.8 ± 11.3 | 74.5 ± 7.7 | [a] | 81.7 ± 12.4 | [a] | [a] |
9d | [a] | 56.0 ± 7.1 | 33.4 ± 6.4 | [b] | [b] | [b] |
10d | 22.0 ± 4.5 | 24.4 ± 3.0 | 14.0 ± 5.6 | 70.3 ± 21.5 | 33.1 ± 9.0 | 42.2 ± 9.3 |
CDDP | 6.0 ± 2.2 | 24.4 ± 4.8 | 2.7 ± 1.0 | 4.4 ± 0.3 | 3.4 ± 0.2 | 10.2 ± 4.8 |
Cpd. | UM-UC-3 | UM-UC-3CDDP | UM-UC-3GEM | UM-UC-3CDDP/GEM | UM-UC-3VBL |
---|---|---|---|---|---|
6b | 23.1 ± 2.6 | 34.6 ± 3.6 | 35.1 ± 2.8 | 32.5 ± 4.0 | 33.8 ± 2.6 |
6c | 7.2 ± 0.6 | 7.8 ± 0.7 | 5.2 ± 0.6 | 8.6 ± 1.4 | 6.0 ± 1.5 |
6d | 4.6 ± 0.4 | 6.4 ± 0.4 | 4.6 ± 0.5 | 6.2 ± 0.8 | 4.9 ± 0.8 |
7a | 56.0 ± 5.7 | 67.7 ± 3.9 | 65.2 ± 4.9 | 62.2 ± 5.3 | 54.9 ± 3.5 |
7b | 13.5 ± 4.5 | 19.0 ± 3.2 | 19.9 ± 3.3 | 17.2 ± 2.1 | 17.3 ± 1.7 |
7c | 6.2 ± 0.8 | 6.8 ± 0.8 | 7.0 ± 0.5 | 5.9 ± 0.4 | 5.8 ± 0.6 |
7d | 6.7 ± 1.4 | 11.2 ± 1.5 | 8.0 ± 2.3 | 9.1 ± 1.2 | 6.3 ± 1.0 |
10d | 30.5 ± 3.7 | 16.6 ± 2.5 | 67.8 ± 9.6 | 25.3 ± 8.0 | 9.4 ± 2.2 |
CDDP | 2.4 ± 0.6 | 26.1 ± 1.8 | 2.6 ± 0.2 | 25.1 ± 1.9 | 2.3 ± 0.3 |
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Lenartowicz, P.; Psurski, M.; Kotynia, A.; Pieniężna, A.; Cuprych, M.; Poniatowska, K.; Brasuń, J.; Kafarski, P. Dipeptides of S-Substituted Dehydrocysteine as Artzyme Building Blocks: Synthesis, Complexing Abilities and Antiproliferative Properties. Int. J. Mol. Sci. 2021, 22, 2168. https://doi.org/10.3390/ijms22042168
Lenartowicz P, Psurski M, Kotynia A, Pieniężna A, Cuprych M, Poniatowska K, Brasuń J, Kafarski P. Dipeptides of S-Substituted Dehydrocysteine as Artzyme Building Blocks: Synthesis, Complexing Abilities and Antiproliferative Properties. International Journal of Molecular Sciences. 2021; 22(4):2168. https://doi.org/10.3390/ijms22042168
Chicago/Turabian StyleLenartowicz, Paweł, Mateusz Psurski, Aleksandra Kotynia, Aleksandra Pieniężna, Monika Cuprych, Klaudia Poniatowska, Justyna Brasuń, and Paweł Kafarski. 2021. "Dipeptides of S-Substituted Dehydrocysteine as Artzyme Building Blocks: Synthesis, Complexing Abilities and Antiproliferative Properties" International Journal of Molecular Sciences 22, no. 4: 2168. https://doi.org/10.3390/ijms22042168