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Open AccessArticle
Small Structural Changes in Chili-Derived Capsaicin Resulting in Nonivamide Analogs of Significantly Improved Cytotoxicity and Good Tumor/Non-Tumor Cell Selectivity
by
Niels V. Heise
Niels V. Heise
,
René Csuk
René Csuk
Thomas Mueller
Thomas Mueller
1
Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes Str. 2, 06120 Halle (Saale), Germany
2
Hematology/Oncology, Medical Faculty, University Clinic for Internal Medicine IV, Martin-Luther University Halle-Wittenberg, Ernst Grube Str. 40, 06120 Halle (Saale), Germany
*
Author to whom correspondence should be addressed.
Molecules 2025, 30(17), 3488; https://doi.org/10.3390/molecules30173488 (registering DOI)
Submission received: 2 July 2025
/
Revised: 11 August 2025
/
Accepted: 21 August 2025
/
Published: 25 August 2025
Abstract
Capsaicin, the major pungent alkaloid in Capsicum species, has been reported to exhibit cytotoxic activity through various mechanisms. In this study, capsaicin and 37 structurally related vanillylamide and ester analogs were synthesized and evaluated for cytotoxic activity and tumor cell/non-tumor cell selectivity in vitro and compared with a Capsicum baccatum (Aji mochero) extract. Seven analogs with superior potency and selectivity compared to capsaicin were identified. Notably, vanillylamides with a C16–C18 chain exhibited IC50 values five-fold lower than capsaicin (15–84 µM), with selectivity indices up to 35. The extract obtained from the dried chili fruit, known to hold capsaicin as its primary component, however, exhibited significantly lower cytotoxic activity against tumor cells than pure capsaicin. These data demonstrate that even minor modifications to the acyl chain (as exemplified for the nonivamide analogs) can enhance the cytotoxicity and selectivity of these derivatives and that isolated compounds are able to offer even greater efficacy than whole-fruit extracts.
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MDPI and ACS Style
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
AMA Style
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 Style
Heise, 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 Style
Heise, 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
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