Small Structural Changes in Chili-Derived Capsaicin Resulting in Nonivamide Analogs of Significantly Improved Cytotoxicity and Good Tumor/Non-Tumor Cell Selectivity
Abstract
1. Introduction
2. Results
2.1. Synthesis
2.2. Biological Evaluation
3. Discussion
4. Materials and Methods
4.1. General
4.2. Synthesis of the Amides 1–37
4.2.1. N-[(4-Hydroxy-3-methoxy)benzyl]pentanamide (1) and 2-methoxy-4-[(pentanoylamino)methyl]phenyl pentanoate (2)
4.2.2. N-[(4-Hydroxy-3-methoxy)benzyl]hexanamide (3) and 2-methoxy-4-[(hexanoylamino)methyl]phenyl hexanoate (4)
4.2.3. N-[(4-Hydroxy-3-methoxy)benzyl]heptanamide (5) and 2-methoxy-4-[(heptanoylamino)methyl]phenyl heptanoate (6)
4.2.4. N-[(4-Hydroxy-3-methoxy)benzyl]octanamide (7) and 2-methoxy-4-[(octanoylamino)methyl]phenyl octanoate (8)
4.2.5. N-[(4-Hydroxy-3-methoxy)benzyl]nonanamide (9) and 2-methoxy-4-[(nonanoylamino)methyl]phenyl nonanoate (10)
4.2.6. N-[(4-Hydroxy-3-methoxy)benzyl]decanamide (11) and 2-methoxy-4-[(decanoylamino)methyl]phenyl decanoate (12)
4.2.7. N-[(4-Hydroxy-3-methoxy)benzyl]undecanamide (13) and 22-methoxy-4-[(undecanoylamino)methyl]phenyl undecanoate (14)
4.2.8. N-[(4-Hydroxy-3-methoxy)benzyl]dodecanamide (15) and 2-methoxy-4-[(dodecanoylamino)methyl]phenyl dodecanoate (16)
4.2.9. N-[(4-Hydroxy-3-methoxy)benzyl]tridecanamide (17) and 2-methoxy-4-[(tridecanoylamino)methyl]phenyl tridecanoate (18)
4.2.10. N-[(4-Hydroxy-3-methoxy)benzyl]tetradecanamide (19) and 2-methoxy-4-[(tetradecanoylamino)methyl]phenyl tetradecanoate (20)
4.2.11. N-[(4-Hydroxy-3-methoxy)benzyl]pentadecanamide (21) and 2-methoxy-4-[(pentadecanoylamino)methyl]phenyl pentadecanoate (22)
4.2.12. N-[(4-Hydroxy-3-methoxy)benzyl]hexadecanamide (23) and 2-methoxy-4-[(hexadecanoylamino)methyl]phenyl hexadecanoate (24)
4.2.13. N-[(4-Hydroxy-3-methoxy)benzyl]heptadecanamide (25) and 2-methoxy-4-[(heptadecanoylamino)methyl]phenyl heptadecanoate (26)
4.2.14. N-[(4-Hydroxy-3-methoxy)benzyl]octadecanamide (27) and 2-methoxy-4-[(octadecanoylamino)methyl]phenyl octadecanoate (28)
4.2.15. N-[(4-Hydroxy-3-methoxy)benzyl]nonadecanamide (29) and 2-methoxy-4-[(nonadecanoylamino)methyl]phenyl nonadecanoate (30)
4.2.16. N-[(4-Hydroxy-3-methoxy)benzyl]icosanamide (31) and 2-methoxy-4-[(icosanoylamino)methyl]phenyl icosanoate (32)
4.2.17. N,N-bis(4-hydroxy-3-methoxybenzyl)nonanamide (33), 4-{[4-hydroxy-3-methoxybenzyl)(nonanoyl)amino]methyl}-2-methoxyphenyl nonanoate (34) and (nonanoylimino) bis(methylene-2-methoxy-4,1-phenylene) dinonanoate (35)
4.2.18. N-[(4-Hydroxy-3-methoxyphenyl)methyl]-2-methyloctanamide (36) and 4-{[(2-methyloctanoyl)amino]methyl}-2-(methyloxy)phenyl 2-methyloctanoate (37)
4.3. Capsaicin
4.4. Preparation of the Chili Extract
4.5. SRB Assay
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Comp. | A2780 | A2780cis | A549 | MCF7 | HT29 | CCD18Co | SI |
---|---|---|---|---|---|---|---|
25 | 2.8 | >100 | 60.5 | 38.4 | 78.5 | >100 | >35.7 |
27 | 3.4 | 76.4 | 50.3 | 32.6 | 42.4 | >100 | >29.0 |
29 | 3.0 | 59.5 | 55.3 | 15.9 | 68.4 | >100 | >33.4 |
A | 15.9 | 84.3 | 70.3 | 42.1 | 51.0 | >100 | >6.3 |
Cell Line | Extract (μg/mL) | Capsaicin A (μg/mL) |
---|---|---|
A2780 | 183.4 | 4.9 |
A2780cis | 460.9 | 25.8 |
A549 | 484.5 | 21.5 |
MCF7 | 232.4 | 12.9 |
HT29 | 309.9 | 15.6 |
CCD18Co | >1250 | >30.5 |
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Heise, N.V.; Csuk, R.; Mueller, T. Small Structural Changes in Chili-Derived Capsaicin Resulting in Nonivamide Analogs of Significantly Improved Cytotoxicity and Good Tumor/Non-Tumor Cell Selectivity. Molecules 2025, 30, 3488. https://doi.org/10.3390/molecules30173488
Heise NV, Csuk R, Mueller T. Small Structural Changes in Chili-Derived Capsaicin Resulting in Nonivamide Analogs of Significantly Improved Cytotoxicity and Good Tumor/Non-Tumor Cell Selectivity. Molecules. 2025; 30(17):3488. https://doi.org/10.3390/molecules30173488
Chicago/Turabian StyleHeise, Niels V., René Csuk, and Thomas Mueller. 2025. "Small Structural Changes in Chili-Derived Capsaicin Resulting in Nonivamide Analogs of Significantly Improved Cytotoxicity and Good Tumor/Non-Tumor Cell Selectivity" Molecules 30, no. 17: 3488. https://doi.org/10.3390/molecules30173488
APA StyleHeise, N. V., Csuk, R., & Mueller, T. (2025). Small Structural Changes in Chili-Derived Capsaicin Resulting in Nonivamide Analogs of Significantly Improved Cytotoxicity and Good Tumor/Non-Tumor Cell Selectivity. Molecules, 30(17), 3488. https://doi.org/10.3390/molecules30173488