Exploring the Mechanism of β-Cyclodextrin-Encased Phenolic Acids Functionalized with TPP for Antioxidant Activity and Targeting
Oxidative stress on the mitochondria in a human cell is attributed to several life-risking conditions, and as such, the importance of molecular structures packed with antioxidant properties and structural characteristics to enter the cell to help prevent such stress has been substantially relevant i...
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MDPI AG
2025-04-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/14/4/465 |
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| author | Christopher Sbarbaro Valeria Márquez-Miranda Matías Leal Ricardo Pino-Rios Pedro Olivares Makarena González Ignacio Díaz-Franulic Fernando González-Nilo Osvaldo Yáñez Yorley Duarte |
| author_facet | Christopher Sbarbaro Valeria Márquez-Miranda Matías Leal Ricardo Pino-Rios Pedro Olivares Makarena González Ignacio Díaz-Franulic Fernando González-Nilo Osvaldo Yáñez Yorley Duarte |
| author_sort | Christopher Sbarbaro |
| collection | DOAJ |
| description | Oxidative stress on the mitochondria in a human cell is attributed to several life-risking conditions, and as such, the importance of molecular structures packed with antioxidant properties and structural characteristics to enter the cell to help prevent such stress has been substantially relevant in recent years. In this study, we investigated the antioxidant properties of triphenylphosphonium (TPP)-conjugated phenolic acids encapsulated in β-cyclodextrin (β-CD). We synthesized TPP conjugates of caffeic, coumaric, and cinnamic acids and formed inclusion complexes with β-CD. Our results showed successful encapsulation of TPP conjugates in β-CD with high efficiency. The TPP conjugates maintained antioxidant activity, with slight reductions observed in β-CD complexes. Furthermore, cell viability studies showed low cytotoxicity of the dds. Computational analyses revealed that TPP conjugation preserved the chemical reactivity of the phenolic acids. Molecular dynamics simulations demonstrated stable inclusion complexes with β-CD and the free energy calculations indicated that TPP conjugation significantly enhanced the ability of caffeic acid to translocate across mitochondrial membranes. These results highlight the potential of TPP-conjugated phenolic acids encapsulated in β-CD as effective antioxidants with improved mitochondrial targeting capabilities. |
| format | Article |
| id | doaj-art-edf6b2c7464e4bd58807a6bda50ccd6e |
| institution | DOAJ |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-edf6b2c7464e4bd58807a6bda50ccd6e2025-08-20T03:14:16ZengMDPI AGAntioxidants2076-39212025-04-0114446510.3390/antiox14040465Exploring the Mechanism of β-Cyclodextrin-Encased Phenolic Acids Functionalized with TPP for Antioxidant Activity and TargetingChristopher Sbarbaro0Valeria Márquez-Miranda1Matías Leal2Ricardo Pino-Rios3Pedro Olivares4Makarena González5Ignacio Díaz-Franulic6Fernando González-Nilo7Osvaldo Yáñez8Yorley Duarte9Center for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago 8370035, ChileCenter for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago 8370035, ChileDepartamento de Química Orgánica y Fisicoquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 8380494, ChileInstituto de Ciencias Exactas y Naturales (ICEN), Universidad Arturo Prat, Playa Brava 3256, Iquique 1111346, ChileCenter for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago 8370035, ChileCenter for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago 8370035, ChileCenter for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago 8370035, ChileCenter for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago 8370035, ChileCentro de Modelación Ambiental y Dinámica de Sistemas (CEMADIS), Universidad de las Américas, Santiago 7500975, ChileCenter for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago 8370035, ChileOxidative stress on the mitochondria in a human cell is attributed to several life-risking conditions, and as such, the importance of molecular structures packed with antioxidant properties and structural characteristics to enter the cell to help prevent such stress has been substantially relevant in recent years. In this study, we investigated the antioxidant properties of triphenylphosphonium (TPP)-conjugated phenolic acids encapsulated in β-cyclodextrin (β-CD). We synthesized TPP conjugates of caffeic, coumaric, and cinnamic acids and formed inclusion complexes with β-CD. Our results showed successful encapsulation of TPP conjugates in β-CD with high efficiency. The TPP conjugates maintained antioxidant activity, with slight reductions observed in β-CD complexes. Furthermore, cell viability studies showed low cytotoxicity of the dds. Computational analyses revealed that TPP conjugation preserved the chemical reactivity of the phenolic acids. Molecular dynamics simulations demonstrated stable inclusion complexes with β-CD and the free energy calculations indicated that TPP conjugation significantly enhanced the ability of caffeic acid to translocate across mitochondrial membranes. These results highlight the potential of TPP-conjugated phenolic acids encapsulated in β-CD as effective antioxidants with improved mitochondrial targeting capabilities.https://www.mdpi.com/2076-3921/14/4/465antioxidantphenolic acidscomplexoxidative stresstriphenylphosphonium (TPP)-conjugated |
| spellingShingle | Christopher Sbarbaro Valeria Márquez-Miranda Matías Leal Ricardo Pino-Rios Pedro Olivares Makarena González Ignacio Díaz-Franulic Fernando González-Nilo Osvaldo Yáñez Yorley Duarte Exploring the Mechanism of β-Cyclodextrin-Encased Phenolic Acids Functionalized with TPP for Antioxidant Activity and Targeting Antioxidants antioxidant phenolic acids complex oxidative stress triphenylphosphonium (TPP)-conjugated |
| title | Exploring the Mechanism of β-Cyclodextrin-Encased Phenolic Acids Functionalized with TPP for Antioxidant Activity and Targeting |
| title_full | Exploring the Mechanism of β-Cyclodextrin-Encased Phenolic Acids Functionalized with TPP for Antioxidant Activity and Targeting |
| title_fullStr | Exploring the Mechanism of β-Cyclodextrin-Encased Phenolic Acids Functionalized with TPP for Antioxidant Activity and Targeting |
| title_full_unstemmed | Exploring the Mechanism of β-Cyclodextrin-Encased Phenolic Acids Functionalized with TPP for Antioxidant Activity and Targeting |
| title_short | Exploring the Mechanism of β-Cyclodextrin-Encased Phenolic Acids Functionalized with TPP for Antioxidant Activity and Targeting |
| title_sort | exploring the mechanism of β cyclodextrin encased phenolic acids functionalized with tpp for antioxidant activity and targeting |
| topic | antioxidant phenolic acids complex oxidative stress triphenylphosphonium (TPP)-conjugated |
| url | https://www.mdpi.com/2076-3921/14/4/465 |
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