Chemical characterization and cardiovascular effects of an oxime derived from a metabolite of Senecio nutans
6 affiliations
- 1Laboratorio de Bioquímica Aplicada, Química y Farmacia, Facultad de Ciencias de la Salud, Universidad Arturo Prat
- 2Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad de Concepción
- 3Instituto Antofagasta (IA), Universidad de Antofagasta
- 4Exercise Applied Physiology Laboratory, Centro de Investigación en Fisiología y Medicina de Altura (FIMEDALT), Departamento Biomédico, Facultad de Ciencias de la Salud, Universidad de Antofagasta
- 5Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid
- 6Biomedical Research and Innovation Centre, School of Science, Engineering and Environment, The University of Salford
Abstract
Senecio nutans Sch. Bip. (Asteraceae) is traditionally used in Andean medicine to alleviate symptoms associated with high-altitude exposure, such as headaches, fatigue, and nausea. Previous studies have identified the p-hydroxyacetophenone derivative 4-hydroxy-3-(isopenten-2-yl) acetophenone (Sn-IV) as a bioactive metabolite with vasodilatory properties. This study aimed to evaluate whether oxime derivatization of Sn-IV enhances its cardiovascular activity and to compare the pharmacological effects of the synthetic oxime derivative OxSn-IV with those of the parent metabolite. OxSn-IV and structurally related oxime derivatives were synthesized from acetophenone precursors. The vascular effects of Sn-IV and OxSn-IV were evaluated in normotensive rats by measuring arterial blood pressure in vivo. Cardiac effects were evaluated in intact hearts (Langendorff), atrial preparations (organ bath), and in isolated ventricular myocytes (photometry). OxSn-IV significantly reduced mean arterial pressure in normotensive rats, whereas the parent metabolite Sn-IV showed minimal effects. OxSn-IV also attenuated the pressor response induced by phenylephrine and reduced heart rate. In isolated hearts, the compound decreased left ventricular pressure, dP/dtmax, and coronary perfusion pressure, showing negative inotropic effects. In isolated atria, OxSn-IV produced a concentration-dependent reduction in beating rate. OxSn-IV produced a negative inotropic effect on systolic calcium levels, thus sarcomere shortening. Oxime derivatization of the natural metabolite Sn-IV markedly enhances its cardiovascular activity. The results provide experimental evidence supporting the traditional use of S. nutans and suggest that oxime derivatives of its metabolites may represent promising scaffolds for the development of new cardiovascular agents.
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BibTeX
@article{palacios2026chemical,
title = {{Chemical characterization and cardiovascular effects of an oxime derived from a metabolite of Senecio nutans}},
author = {Javier Palacios and Claudio Parra and Adrián Paredes and Fredi Cifuentes and David C. Andrade and Ángel Luis García-Villalón and David J. Greensmith and Mario Espinoza-Gatica and Tamara Sáez and Rienzi Díaz-Navarro},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-61925-5},
url = {https://doi.org/10.1038/s41598-026-61925-5},
note = {CC BY},
}
RIS
TY - JOUR
TI - Chemical characterization and cardiovascular effects of an oxime derived from a metabolite of Senecio nutans
AU - Javier Palacios
AU - Claudio Parra
AU - Adrián Paredes
AU - Fredi Cifuentes
AU - David C. Andrade
AU - Ángel Luis García-Villalón
AU - David J. Greensmith
AU - Mario Espinoza-Gatica
AU - Tamara Sáez
AU - Rienzi Díaz-Navarro
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-61925-5
UR - https://doi.org/10.1038/s41598-026-61925-5
AB - Senecio nutans Sch. Bip. (Asteraceae) is traditionally used in Andean medicine to alleviate symptoms associated with high-altitude exposure, such as headaches, fatigue, and nausea. Previous studies have identified the p-hydroxyacetophenone derivative 4-hydroxy-3-(isopenten-2-yl) acetophenone (Sn-IV) as a bioactive metabolite with vasodilatory properties. This study aimed to evaluate whether oxime derivatization of Sn-IV enhances its cardiovascular activity and to compare the pharmacological effects of the synthetic oxime derivative OxSn-IV with those of the parent metabolite. OxSn-IV and structurally related oxime derivatives were synthesized from acetophenone precursors. The vascular effects of Sn-IV and OxSn-IV were evaluated in normotensive rats by measuring arterial blood pressure in vivo. Cardiac effects were evaluated in intact hearts (Langendorff), atrial preparations (organ bath), and in isolated ventricular myocytes (photometry). OxSn-IV significantly reduced mean arterial pressure in normotensive rats, whereas the parent metabolite Sn-IV showed minimal effects. OxSn-IV also attenuated the pressor response induced by phenylephrine and reduced heart rate. In isolated hearts, the compound decreased left ventricular pressure, dP/dtmax, and coronary perfusion pressure, showing negative inotropic effects. In isolated atria, OxSn-IV produced a concentration-dependent reduction in beating rate. OxSn-IV produced a negative inotropic effect on systolic calcium levels, thus sarcomere shortening. Oxime derivatization of the natural metabolite Sn-IV markedly enhances its cardiovascular activity. The results provide experimental evidence supporting the traditional use of S. nutans and suggest that oxime derivatives of its metabolites may represent promising scaffolds for the development of new cardiovascular agents.
SN - 2045-2322
ER -