Abstract
Background: The aminocoumarin antibiotic, novobiocin, is a natural product that inhibits DNA gyrase, a bacterial enzyme involved in cell division.
Method: More recently, novobiocin was found to act also on eukaryotic cells by blocking the 90 kDa heat shock protein (Hsp90). Hsp90 is a molecular chaperone, critical for folding, stabilization and activation of many proteins, in particular oncoproteins responsible for cancer progression. As opposed to the geldanamycin and radicicol, the known inhibitors of Hsp90 that bind to the N-terminal region, the binding domain of novobiocin is localized in the C-terminal part of this protein. While the N-terminal inhibition also leads to the induction of some pro-survival signals, C-terminal inhibitors in which prosurvival responses are avoided and client degradation is maintained can be developed as a new class of potential anticancer chemotherapeutics. Numerous novobiocin analogs have been designed in the search for more potent compounds and some of them exhibit significantly enhanced anti-proliferative activity versus the natural product, as evaluated by cellular efficacies against several cancer cell lines. Conclusion: This review describes structure-activity-relationships of novobiocin analogs and some biological data reported so far on the anticancer activity of these modified compounds.Keywords: Antiproliferative activity, chemical modifications, heat shock protein, protein chaperone, structure-activity relationship.
Mini-Reviews in Medicinal Chemistry
Title:Novobiocin Analogs as Potential Anticancer Agents
Volume: 17 Issue: 9
Author(s): Angelika Dlugosz and Anna Janecka*
Affiliation:
- Department of Biomolecular Chemistry, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz,Poland
Keywords: Antiproliferative activity, chemical modifications, heat shock protein, protein chaperone, structure-activity relationship.
Abstract: Background: The aminocoumarin antibiotic, novobiocin, is a natural product that inhibits DNA gyrase, a bacterial enzyme involved in cell division.
Method: More recently, novobiocin was found to act also on eukaryotic cells by blocking the 90 kDa heat shock protein (Hsp90). Hsp90 is a molecular chaperone, critical for folding, stabilization and activation of many proteins, in particular oncoproteins responsible for cancer progression. As opposed to the geldanamycin and radicicol, the known inhibitors of Hsp90 that bind to the N-terminal region, the binding domain of novobiocin is localized in the C-terminal part of this protein. While the N-terminal inhibition also leads to the induction of some pro-survival signals, C-terminal inhibitors in which prosurvival responses are avoided and client degradation is maintained can be developed as a new class of potential anticancer chemotherapeutics. Numerous novobiocin analogs have been designed in the search for more potent compounds and some of them exhibit significantly enhanced anti-proliferative activity versus the natural product, as evaluated by cellular efficacies against several cancer cell lines. Conclusion: This review describes structure-activity-relationships of novobiocin analogs and some biological data reported so far on the anticancer activity of these modified compounds.Export Options
About this article
Cite this article as:
Dlugosz Angelika and Janecka Anna*, Novobiocin Analogs as Potential Anticancer Agents, Mini-Reviews in Medicinal Chemistry 2017; 17 (9) . https://dx.doi.org/10.2174/1389557516666161223155525
DOI https://dx.doi.org/10.2174/1389557516666161223155525 |
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
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
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...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
-
microRNA Biogenesis Pathway as a Therapeutic Target for Human Disease and Cancer
Current Pharmaceutical Design Chemoprevention with Phytonutrients and Microalgae Products in Chronic Inflammation and Colon Cancer
Current Pharmaceutical Design Introduction: MMPs, ADAMs/ADAMTSs Research Products to Achieve Big Dream
Anti-Cancer Agents in Medicinal Chemistry The Mast Cell Pathway to Inflammation and Homeostasis: Pharmacolo- gical Insights
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Targeting Angiogenic Pathways in Colorectal Cancer: Complexities, Challenges and Future Directions
Current Drug Targets Poly (Lactic-co-Glycolic Acid) & Tocopheryl Polyethylene Glycol Succinate Nanoparticles for the Treatment of Different Brain Cancers
Anti-Cancer Agents in Medicinal Chemistry Prediction of Disease-Related Genes Based on Hybrid Features
Current Proteomics CD44 and EpCAM: Cancer-Initiating Cell Markers
Current Molecular Medicine Pharmacogenomics Opportunities in Nuclear Receptor Targeted Cancer Therapy
Current Cancer Drug Targets PEDF as an Emerging Therapeutic Candidate for Osteosarcoma
Current Cancer Drug Targets Merging Transport Data for Choroid Plexus with Blood-Brain Barrier to Model CNS Homeostasis and Disease More Effectively
CNS & Neurological Disorders - Drug Targets Recent Advances in GNAS Epigenetic Research of Pseudohypoparathyroidism
Current Molecular Medicine Alphavirus Vectors for Gene Therapy Applications
Current Gene Therapy BRCA1 as Target for Breast Cancer Prevention and Therapy
Anti-Cancer Agents in Medicinal Chemistry Phosphoinositide 3-Kinases as Targets for Therapeutic Intervention
Current Pharmaceutical Design Chemoprevention Gene Therapy (CGT) of Pancreatic Cancer Using Perillyl Alcohol and a Novel Chimeric Serotype Cancer Terminator Virus
Current Molecular Medicine Natural Products as Anti-Cancerous Therapeutic Molecules Targeted towards Topoisomerases
Current Protein & Peptide Science Novel Agents in Anticancer Drug Therapy I (Antiangiogenic Agents, Egfr Inhibitors)
Medicinal Chemistry Reviews - Online (Discontinued) Mapping the High Throughput SEREX Technology Screening for Novel Tumor Antigens
Combinatorial Chemistry & High Throughput Screening Glycyrrhetinic Acid and Its Derivatives: Anti-Cancer and Cancer Chemopreventive Properties, Mechanisms of Action and Structure- Cytotoxic Activity Relationship
Current Medicinal Chemistry