Abstract
The thiol or sulfhydryl group, as part of low molecular weight non-peptide biomolecules, as well as part of the cysteine residues in peptides and proteins, is known to play extremely important roles in several aspects of cellular function. Glutathione (γ-Glu-Cys-Gly; GSH) is the most abundant thiol-containing peptide in mammals, being present intracellularly in the low millimolar concentration range, but only in the low micromolar concentration range in the majority of extracellular fluids. Notably, intracellular levels of GSH have been found to be significantly upregulated in a number of human cancers, a phenomenon thought to contribute, in concert with overexpression of some GSHassociated enzymes, to the development of tumor cell chemo- and radioresistance. On the other hand, various natural and synthetic chemical entities of different sizes show significant cytotoxic activity only upon interaction with a thiol, and can therefore exploit the GSH-rich intracellular environment of tumors. This review article attempts to summarize the current structural and pharmacological knowledge in the field of thiol-activated anticancer agents, with a focus on the mechanism(s) of their activation. Even though a great part of the available thiol-activated anticancer compounds is still in the preclinical phase of testing, some of them are undergoing trials in cancer patients.
Keywords: Thiols, glutathione, thiol-mediated prodrug activation, cancer, chemotherapy, drug targeting.
Anti-Cancer Agents in Medicinal Chemistry
Title:Thiol-Activated Anticancer Agents: The State of the Art
Volume: 17 Issue: 1
Author(s): Daniele Dalzoppo, Veronica Di Paolo, Laura Calderan, Gianfranco Pasut, Antonio Rosato, Anna Maria Caccuri and Luigi Quintieri
Affiliation:
Keywords: Thiols, glutathione, thiol-mediated prodrug activation, cancer, chemotherapy, drug targeting.
Abstract: The thiol or sulfhydryl group, as part of low molecular weight non-peptide biomolecules, as well as part of the cysteine residues in peptides and proteins, is known to play extremely important roles in several aspects of cellular function. Glutathione (γ-Glu-Cys-Gly; GSH) is the most abundant thiol-containing peptide in mammals, being present intracellularly in the low millimolar concentration range, but only in the low micromolar concentration range in the majority of extracellular fluids. Notably, intracellular levels of GSH have been found to be significantly upregulated in a number of human cancers, a phenomenon thought to contribute, in concert with overexpression of some GSHassociated enzymes, to the development of tumor cell chemo- and radioresistance. On the other hand, various natural and synthetic chemical entities of different sizes show significant cytotoxic activity only upon interaction with a thiol, and can therefore exploit the GSH-rich intracellular environment of tumors. This review article attempts to summarize the current structural and pharmacological knowledge in the field of thiol-activated anticancer agents, with a focus on the mechanism(s) of their activation. Even though a great part of the available thiol-activated anticancer compounds is still in the preclinical phase of testing, some of them are undergoing trials in cancer patients.
Export Options
About this article
Cite this article as:
Dalzoppo Daniele, Paolo Di Veronica, Calderan Laura, Pasut Gianfranco, Rosato Antonio, Caccuri Maria Anna and Quintieri Luigi, Thiol-Activated Anticancer Agents: The State of the Art, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (1) . https://dx.doi.org/10.2174/1871520616666160817110310
DOI https://dx.doi.org/10.2174/1871520616666160817110310 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Preface: [Hot topic: Metal Compounds in Medicinal Chemistry (Executive Editor: Dinorah Gambino)]
Mini-Reviews in Medicinal Chemistry Snake Venom Derived Molecules in Tumor Angiogenesis and its Application in Cancer Therapy; An Overview
Current Topics in Medicinal Chemistry Computer Aided Detection and Screening of Thyroid Cancer Using ANFIS Classifier
Current Medical Imaging Nanosized Tamoxifen-Porphyrin-Glucose [TPG] Conjugate: Novel Selective Anti-breast-cancer Agent, Synthesis and In Vitro Evaluations
Medicinal Chemistry Microcirculation in Sepsis: New Perspectives
Current Vascular Pharmacology Soy Phytoestrogens and Breast Cancer Chemoprevention: Molecular Mechanisms
Current Nutrition & Food Science Insights into Ecto-5’-Nucleotidase as a New Target for Cancer Therapy: A Medicinal Chemistry Study
Current Medicinal Chemistry Polymeric Nanoparticles of FMISO: Are Nano-Radiopharmaceuticals Better Than Conventional Ones?
Current Radiopharmaceuticals Clinical Impact of Gastric Acid Suppressants Use on the Efficacy of Gefitinib in Patients with Advanced Adenocarcinoma of the Lung Harboring Common EGFR Mutations
Clinical Cancer Drugs Patent Selections
Recent Patents on Anti-Cancer Drug Discovery Sunscreening and Photosensitizing Properties of Coumarins and their Derivatives
Letters in Drug Design & Discovery Edelfosine: An Antitumor Drug Prototype
Anti-Cancer Agents in Medicinal Chemistry Treatment of Elderly Patients Affected by Lung Cancer: Why to Treat, when to Treat and what we Know
Anti-Cancer Agents in Medicinal Chemistry Novel Inhibitors of DNA Repair Enzyme TDP1 Combining Monoterpenoid and Adamantane Fragments
Anti-Cancer Agents in Medicinal Chemistry Aspirin: A Potential Therapeutic Approach in Pancreatic Cancer
Current Medicinal Chemistry A Classification Method for Microarrays Based on Diversity
Current Bioinformatics Current Status and Perspectives in Peptide Receptor Radiation Therapy
Current Pharmaceutical Design Nanocarriers as Tools in Delivering Active Compounds for Immune System Related Pathologies
Recent Patents on Nanotechnology Peptidyl Prolyl Isomerase, Pin1 is a Potential Target for Enhancing the Therapeutic Efficacy of Etoposide
Current Cancer Drug Targets Long Circulating Polymeric Nanoparticles for Gene/Drug Delivery
Current Drug Metabolism