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Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases
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Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases

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Glutathione Transferase (GST)-Activated Prodrugs

Paolo Ruzza1, Andrea Calderan

  • 1Institute of Biomolecular Chemistry of CNR, Padova Unit, Via Marzolo 1, Padova 35131, Italy. paolo.ruzza@unipd.it.

Pharmaceutics
|December 5, 2013
PubMed

Insights

Glutathione transferase (GST) enzymes inactivate anticancer drugs. Overexpression of GSTs, like GSTP1-1, causes drug resistance, driving research into GST inhibitors and prodrugs.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Oncology

Background:

  • Glutathione transferase (GST) enzymes catalyze the detoxification of electrophilic compounds.
  • GSTs, particularly GSTP1-1, are implicated in anticancer drug resistance.
  • Tumor overexpression of GSTs presents a therapeutic challenge in cancer treatment.

Purpose of the Study:

  • To review the structural and pharmacological aspects of GST-activated cytotoxic compounds.
  • To explore the role of GSTs in drug resistance and potential therapeutic strategies.
  • To provide an overview of current knowledge on targeting GSTs in cancer therapy.

Main Methods:

  • Literature review of structural and pharmacological data on GST-activated compounds.
  • Analysis of studies linking GST overexpression to anticancer drug resistance.
  • Synthesis of information on GST inhibitors and GST-activated prodrugs.

Main Results:

  • GSTs conjugate glutathione to electrophilic anticancer agents, leading to their inactivation.
  • Overexpression of specific GSTs, such as GSTP1-1, correlates with resistance to diverse anticancer drugs.
  • The understanding of GST structure-activity relationships informs the design of targeted therapies.

Conclusions:

  • GSTs play a significant role in both drug metabolism and resistance.
  • Targeting GSTs through inhibition or activation offers potential strategies to overcome drug resistance.
  • Further research into GST-activated cytotoxic compounds is warranted for novel cancer therapeutics.

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