Abstract
Various classes of cytotoxic compounds which alkylate cellular thiols are described namely α, β-unsaturated ketones, α-methylene-γ -lactones, azines of Mannich bases, imexon, isothiocyanates, a benzoacronycine as well as activation by thiols prior to alkylation. The mechanisms of action of some of the molecules, such as the formation of reactive oxygen species, are presented. The cytotoxicity of a number of drugs can be influenced by modulation of the concentration of thiols including the observation that potencies can be increased by thiol activation. The ability of certain thiol reagents to reverse multidrug resistance as well as some miscellaneous actions of thiol alkylators are described.
Keywords: Thiols, alkylating agents, α,β-unsaturated ketones, αmethylene-γ-lactones, azines, imexon, isothiocyanates, benzoacronycine, tumour sensitization, drug resistance
Mini-Reviews in Medicinal Chemistry
Title: Cytotoxic Thiol Alkylators
Volume: 7 Issue: 2
Author(s): Hari N. Pati, Umashankar Das, Rajendra K. Sharma and Jonathan R. Dimmock
Affiliation:
Keywords: Thiols, alkylating agents, α,β-unsaturated ketones, αmethylene-γ-lactones, azines, imexon, isothiocyanates, benzoacronycine, tumour sensitization, drug resistance
Abstract: Various classes of cytotoxic compounds which alkylate cellular thiols are described namely α, β-unsaturated ketones, α-methylene-γ -lactones, azines of Mannich bases, imexon, isothiocyanates, a benzoacronycine as well as activation by thiols prior to alkylation. The mechanisms of action of some of the molecules, such as the formation of reactive oxygen species, are presented. The cytotoxicity of a number of drugs can be influenced by modulation of the concentration of thiols including the observation that potencies can be increased by thiol activation. The ability of certain thiol reagents to reverse multidrug resistance as well as some miscellaneous actions of thiol alkylators are described.
Export Options
About this article
Cite this article as:
Pati N. Hari, Das Umashankar, Sharma K. Rajendra and Dimmock R. Jonathan, Cytotoxic Thiol Alkylators, Mini-Reviews in Medicinal Chemistry 2007; 7 (2) . https://dx.doi.org/10.2174/138955707779802642
DOI https://dx.doi.org/10.2174/138955707779802642 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...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
-
Magnetic Nanoparticles in Brain Disease Diagnosis and Targeting Drug Delivery
Current Nanoscience Extracellular Tropomyosin: A Novel Common Pathway Target for Anti- Angiogenic Therapy
Current Cancer Drug Targets Graphical Abstracts
Letters in Organic Chemistry Target Genetic Abnormalities for the Treatment of Colon Cancer and Its Progression to Metastasis
Current Drug Targets Iontophoresis: Drug Delivery System by Applying an Electrical Potential Across the Skin
Drug Delivery Letters Smart Polymers and Their Role in Drug Delivery: A Review
Current Drug Therapy Effect of SDF-1 α on Endogenous Mobilized and Transplanted Stem Cells in Regeneration after Myocardial Infarction
Current Pharmaceutical Design Transition Metal-Based Prodrugs for Anticancer Drug Delivery
Current Medicinal Chemistry Dendritic Cells and their Receptors in Antitumor Immune Response
Current Molecular Medicine Potential Crossreactivity of Human Immune Responses Against HCMV Glycoprotein B
Current Drug Discovery Technologies An Update on JAK Inhibitors
Current Medicinal Chemistry Parthenogenetic Cell Lines: An Unstable Equilibrium Between Pluripotency and Malignant Transformation
Current Pharmaceutical Biotechnology Recombinant Human p53 Adenovirus Injection (rAd-p53) Combined with Chemotherapy for 4 Cases of High-grade Serous Ovarian Cancer
Current Gene Therapy The Chemokine System as a Therapeutic Target in Autoimmune Thyroid Diseases: A Focus on the Interferon-γ Inducible Chemokines and their Receptor
Current Pharmaceutical Design Human Cytomegalovirus US28: A Functionally Selective Chemokine Binding Receptor
Infectious Disorders - Drug Targets Tankyrase as a Novel Molecular Target in Cancer and Fibrotic Diseases
Current Drug Targets Copper Compounds in Cancer Chemotherapy
Current Medicinal Chemistry Integrase Interactor 1 in Health and Disease
Current Protein & Peptide Science Anticancer Drug Design Using Scaffolds of β-Lactams, Sulfonamides, Quinoline, Quinoxaline and Natural Products. Drugs Advances in Clinical Trials
Current Medicinal Chemistry Interferon-Beta Therapy Monitoring in Multiple Sclerosis Patients
Endocrine, Metabolic & Immune Disorders - Drug Targets