Abstract
Mitochondrial dysfunction, either inherited or acquired, is associated with several diseases in humans. Depending on the cell type and location, cells are prone to multiple types of insults that may compromise their proper function. Generally, these insults are overcome by defensive mechanisms but sometimes they lead to sustained damage, requiring the action of scavenging and repair machineries to retain the viability of the cells. As a final measure, severely damaged cells are targeted to a controlled cell death pathway in order to not to compromise the well-being of the whole tissue.
The polyamines, spermine and spermidine are essential cellular constituents, participating in many vital functions such as proliferation and differentiation, immune response and scavenging of reactive oxygen species. Therefore, dysregulation of polyamine metabolism is often associated with different pathological states. Polyamine acetylating enzyme spermidine/spermine-N1-acetyltransferase is induced by inflammation, drugs and by several other environmental insults. Resulting accelerated polyamine acetylation with accompanying polyamine biosynthesis induction i.e. activation of polyamine futile cycle generates excessive amount of hydrogen peroxide, hampers cell energy metabolism and induces mitochondrial dysfunction and biogenesis. Therefore, the drugs inhibiting polyamine metabolism are valuable in protecting mitochondria and cell energy metabolism. Here we review the current literature focusing on the applicability of chargedeficient polyamine analogs as drugs to modulate polyamine metabolism. Alteration of pKa of amino group(s) in a respective analog is achieved by fluorine substitution of hydrogen atom, hydroxylamine substitution of methylamine or by reducing the numbers of carbon atoms between amine groups to two instead of three or four.
Keywords: Cell organelles, charge deficient, ornithine decarboxylase, polyamine, polyamine analog, reactive oxygen species.
Current Pharmaceutical Design
Title:Charge Deficient Analogues of the Natural Polyamines
Volume: 20 Issue: 2
Author(s): Janne Weisell, Mervi T. Hyvonen, Leena Alhonen, Jouko Vepsalainen, Tuomo A. Keinanen and Alex R. Khomutov
Affiliation:
Keywords: Cell organelles, charge deficient, ornithine decarboxylase, polyamine, polyamine analog, reactive oxygen species.
Abstract: Mitochondrial dysfunction, either inherited or acquired, is associated with several diseases in humans. Depending on the cell type and location, cells are prone to multiple types of insults that may compromise their proper function. Generally, these insults are overcome by defensive mechanisms but sometimes they lead to sustained damage, requiring the action of scavenging and repair machineries to retain the viability of the cells. As a final measure, severely damaged cells are targeted to a controlled cell death pathway in order to not to compromise the well-being of the whole tissue.
The polyamines, spermine and spermidine are essential cellular constituents, participating in many vital functions such as proliferation and differentiation, immune response and scavenging of reactive oxygen species. Therefore, dysregulation of polyamine metabolism is often associated with different pathological states. Polyamine acetylating enzyme spermidine/spermine-N1-acetyltransferase is induced by inflammation, drugs and by several other environmental insults. Resulting accelerated polyamine acetylation with accompanying polyamine biosynthesis induction i.e. activation of polyamine futile cycle generates excessive amount of hydrogen peroxide, hampers cell energy metabolism and induces mitochondrial dysfunction and biogenesis. Therefore, the drugs inhibiting polyamine metabolism are valuable in protecting mitochondria and cell energy metabolism. Here we review the current literature focusing on the applicability of chargedeficient polyamine analogs as drugs to modulate polyamine metabolism. Alteration of pKa of amino group(s) in a respective analog is achieved by fluorine substitution of hydrogen atom, hydroxylamine substitution of methylamine or by reducing the numbers of carbon atoms between amine groups to two instead of three or four.
Export Options
About this article
Cite this article as:
Weisell Janne, Hyvonen T. Mervi, Alhonen Leena, Vepsalainen Jouko, Keinanen A. Tuomo and Khomutov R. Alex, Charge Deficient Analogues of the Natural Polyamines, Current Pharmaceutical Design 2014; 20 (2) . https://dx.doi.org/10.2174/13816128113199990037
DOI https://dx.doi.org/10.2174/13816128113199990037 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
Association of Oxidative Stress to the Genesis of Anxiety: Implications for Possible Therapeutic Interventions
Current Neuropharmacology Evolutioninthe Pharmacogenetics and Pharmacogenomics of Inflammatory Bowel Disease - Order Slowly Rises from the Chaos
Current Pharmacogenomics Synthesis and Biological Evaluation of New Piperazine Substituted 3, 5-Diarylisoxazolines
Current Organic Synthesis Pyrimidine Nucleosides in Molecular PET Imaging of Tumor Proliferation
Current Medicinal Chemistry Integrins: A Method of Early Intervention in the Treatment of Colorectal Liver Metastases
Current Pharmaceutical Design Phosphotyrosine Phosphatases in Cancer Diagnostic and Treatment
Recent Patents on DNA & Gene Sequences Updates on the Role of FDG-PET/CT in Gynecological Malignancies
Current Molecular Imaging (Discontinued) An Overview on Keratinocyte Growth Factor: From the Molecular Properties to Clinical Applications
Protein & Peptide Letters Safety of Dipeptidyl Peptidase 4 Inhibitors for Treatment of Type 2 Diabetes
Current Drug Safety Cancer Diagnosis and Disease Gene Identification <i>via</i> Statistical Machine Learning
Current Bioinformatics Drug-Drug Interactions of Triazole Antifungal Agents in Multimorbid Patients and Implications for Patient Care
Current Drug Metabolism Progress in the Discovery of Macrocyclic Histone Deacetylase Inhibitors for the Treatment of Cancer
Current Medicinal Chemistry Review on Triggered Liposomal Drug Delivery with a Focus on Ultrasound
Current Cancer Drug Targets Artificial Intelligence, Big Data and Machine Learning Approaches in Precision Medicine & Drug Discovery
Current Drug Targets 1,3,5-Triazine Analogs: A Potent Anticancer Scaffold
Current Signal Transduction Therapy Let-7a Could Serve as A Biomarker for Chemo-Responsiveness to Docetaxel in Gastric Cancer
Anti-Cancer Agents in Medicinal Chemistry A Perspective on Clinical Islet Transplantation: Past, Present and Developments for Future
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Predicting Inhibitors for Multidrug Resistance Associated Protein-2 Transporter by Machine Learning Approach
Combinatorial Chemistry & High Throughput Screening Cachexia and Herbal Medicine: Perspective
Current Pharmaceutical Design IBD Modern Concepts, Nano Drug Delivery and Patents: An Update
Recent Patents on Nanomedicine