Publication:
Antimigratory Effect of Lipophilic Cations Derived from Gallic and Gentisic Acid and Synergistic Effect with 5-Fluorouracil on Metastatic Colorectal Cancer Cells: A New Synthesis Route

Simple item page
dc.contributor.authorSuárez, Cristian
dc.contributor.authorJara, José
dc.contributor.authorCortés, Gonzalo
dc.contributor.authorRojas, Diego
dc.contributor.authorAraya, Gabriel
dc.contributor.authorMolina, Alfredo
dc.contributor.authorGonzález, Fabiola
dc.contributor.authorFuentes, Sebastián
dc.contributor.authorAránguiz, Pablo
dc.contributor.authorCampodónico, Paola
dc.contributor.authorMaya, Juan
dc.contributor.authorVivar, Raúl
dc.contributor.authorCatalán, Mabel
dc.date.accessioned2025-01-16T14:24:13Z
dc.date.available2025-01-16T14:24:13Z
dc.date.issued2024
dc.description.abstractColorectal cancer (CRC) is the third leading cause of cancer deaths in the world. Standard drugs currently used for the treatment of advanced CRC-such as 5-fluorouracil (5FU)-remain unsatisfactory in their results due to their high toxicity, high resistance, and adverse effects. In recent years, mitochondria have become an attractive target for cancer therapy due to higher transmembrane mitochondrial potential. We synthesized gallic acid derivatives linked to a ten-carbon aliphatic chain associated with triphenylphosphonium (TPP+C10), a lipophilic cationic molecule that induces the uncoupling of the electron transport chain (ETC). Other derivatives, such as gentisic acid (GA-TPP+C10), have the same effects on colorectal cancer cells. Although part of our group had previously reported preparing these structures by a convergent synthesis route, including their application via flow chemistry, there was no precedent for a new methodology for preparing these compounds. In this scenario, this study aims to develop a new linear synthesis strategy involving an essential step of Steglich esterification under mild conditions (open flask) and a high degree of reproducibility. Moreover, the study seeks to associate GA-TPP+C10 with 5FU to evaluate synergistic antineoplastic effects. In addition, we assess the antimigratory effect of GA-TPP+C10 and TPP+C10 using human and mouse metastatic CRC cell lines. The results show a new and efficient synthesis route of these compounds, having synergistic effects in combination with 5FU, increasing apoptosis and enhancing cytotoxic properties. Additionally, the results show a robust antimigratory effect of GATPP+C10 and TPP+C10, reducing the activation pathways linked to tumor progression and reducing the expression of VEGF and MMP-2 and MMP-9, common biomarkers of advanced CRC. Moreover, TPP+C10 and GA-TPP+C10 increase the activity of metabolic signaling pathways through AMPK activation. The data allow us to conclude that these compounds can be used for in vivo evaluations and are a promising alternative associated with conventional therapies for advanced colorectal cancer. Additionally, the reported intermediates of the new synthesis route could give rise to analog compounds with improved therapeutic activity.
dc.description.versionVersión Publicada
dc.identifier.citationSuárez-Rozas C, Jara JA, Cortés G, Rojas D, Araya-Valdés G, Molina-Berrios A, González-Herrera F, Fuentes-Retamal S, Aránguiz-Urroz P, Campodónico PR, Maya JD, Vivar R, Catalán M. Antimigratory Effect of Lipophilic Cations Derived from Gallic and Gentisic Acid and Synergistic Effect with 5-Fluorouracil on Metastatic Colorectal Cancer Cells: A New Synthesis Route. Cancers (Basel). 2024 Aug 27;16(17):2980. doi: 10.3390/cancers16172980
dc.identifier.doihttps://doi.org/10.3390/cancers16172980
dc.identifier.urihttps://hdl.handle.net/11447/9661
dc.language.isoen
dc.subject5-fluorouracil
dc.subjectSynergism
dc.subjectAnticancer effect
dc.subjectantimigratory effect
dc.subjectcolorectal cancer
dc.subjectGallic and gentisic acid derivatives
dc.subjectlLipophilic cations
dc.subjectTargeting mitochondria
dc.titleAntimigratory Effect of Lipophilic Cations Derived from Gallic and Gentisic Acid and Synergistic Effect with 5-Fluorouracil on Metastatic Colorectal Cancer Cells: A New Synthesis Route
dc.typeArticle
dcterms.accessRightsAcceso Abierto
dcterms.sourceCancers
dspace.entity.typePublication

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Antimigratory Effect of Lipophilic Cations Derived from Gallicand Gentisic Acid and Synergistic Effect with 5-Fluorouracil.pdf
Size:
5.56 MB
Format:
Adobe Portable Document Format
Description:
Texto Completo
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
347 B
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Artículos Medicina y Ciencias de la Salud

Implementado por OpenGeek Services