Resveratrol derivatives as a pharmacological tool
Lucia Biasutto1,2, Andrea Mattarei3,4, Michele Azzolini1,2
1CNR Neuroscience Institute, Padova, Italy.
Annals of the New York Academy of Sciences
|July 5, 2017
Summary
Resveratrol prodrugs aim to enhance bioavailability by improving solubility, absorption, and metabolism. Mitochondria-targeted derivatives show promise for selective cancer cell killing, suggesting anticancer applications.
Area of Science:
- Pharmacology and Medicinal Chemistry
- Drug Development
- Cancer Therapeutics
Background:
- Resveratrol, a natural polyphenol, exhibits various health benefits but suffers from poor bioavailability.
- Developing resveratrol prodrugs is crucial to overcome limitations like low solubility and rapid metabolism.
- Enhancing resveratrol's therapeutic potential requires strategies to improve its pharmacokinetic and pharmacodynamic properties.
Purpose of the Study:
- To explore strategies for developing effective resveratrol prodrugs.
- To investigate methods for modulating resveratrol's physical properties and body distribution.
- To evaluate the potential of targeted resveratrol derivatives, particularly mitochondria-targeted ones, for anticancer applications.
Main Methods:
- Chemical modification of resveratrol to create prodrugs with altered properties (e.g., solubility, absorption, metabolism).
- Utilizing functionalization via carboxyester, acetal, and carbamate linkages.
- Developing subcellular site-specific derivatives, such as mitochondria-targeted resveratrol.
Main Results:
- Prodrug strategies focus on improving water solubility, altering body distribution, enhancing gastrointestinal absorption, and hindering phase II metabolism to increase bioavailability.
- Mitochondria-targeted resveratrol derivatives demonstrated in vitro pro-oxidant and cytotoxic effects.
- These targeted derivatives selectively killed fast-growing and tumor cells at low micromolar concentrations.
Conclusions:
- Resveratrol prodrug development offers promising avenues for enhancing its therapeutic efficacy.
- Mitochondria-targeted resveratrol derivatives exhibit potent anticancer activity in vitro.
- Further research into these targeted prodrugs could lead to novel cancer treatment strategies.
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