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Published on: September 10, 2021
The Effects of Synthetically Modified Natural Compounds on ABC Transporters
Daniel Dantzic1, Pawan Noel2, Fabrice Merien3,4
1School of Science, Auckland University of Technology, Auckland 1010, New Zealand. daniel.dantzic@aut.ac.nz.
Abstract:
Multidrug resistance (MDR) is a major hurdle which must be overcome to effectively treat cancer. ATP-binding cassette transporters (ABC transporters) play pivotal roles in drug absorption and disposition, and overexpression of ABC transporters has been shown to attenuate cellular/tissue drug accumulation and thus increase MDR across a variety of cancers. Overcoming MDR is one desired approach to improving the survival rate of patients. To date, a number of modulators have been identified which block the function and/or decrease the expression of ABC transporters, thereby restoring the efficacy of a range of anticancer drugs. However, clinical MDR reversal agents have thus far proven ineffective and/or toxic. The need for new, effective, well-tolerated and nontoxic compounds has led to the development of natural compounds and their derivatives to ameliorate MDR. This review evaluates whether synthetically modifying natural compounds is a viable strategy to generate potent, nontoxic, ABC transporter inhibitors which may potentially reverse MDR.
Insights
Synthetically modifying natural compounds may yield potent, non-toxic inhibitors of ATP-binding cassette (ABC) transporters, offering a promising strategy to overcome multidrug resistance (MDR) in cancer treatment.
Area of Science:
- Pharmacology
- Oncology
- Biochemistry
Background:
- Multidrug resistance (MDR) significantly impedes effective cancer chemotherapy.
- Overexpression of ATP-binding cassette (ABC) transporters is a primary mechanism driving MDR by reducing intracellular drug accumulation.
- Current MDR reversal agents often exhibit toxicity and limited clinical efficacy.
Purpose of the Study:
- To evaluate the potential of synthetically modified natural compounds as novel agents to combat MDR.
- To explore the development of potent and non-toxic inhibitors targeting ABC transporters.
Main Methods:
- Review of existing literature on natural compounds and their derivatives.
- Analysis of synthetic modification strategies for natural products.
- Assessment of ABC transporter inhibition and MDR reversal capabilities.
Main Results:
- Natural compounds and their derivatives show promise in modulating ABC transporter function and expression.
- Synthetic modifications can enhance the potency and reduce the toxicity of these compounds.
- This approach offers a viable pathway to develop effective MDR reversal agents.
Conclusions:
- Synthetic modification of natural compounds represents a promising strategy for generating effective, well-tolerated, and non-toxic inhibitors of ABC transporters.
- This approach holds potential for overcoming multidrug resistance and improving cancer treatment outcomes.
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