Abstract
The mitochondrion’s negatively charged membrane potential has been well documented to drive the accumulation of membrane permeable delocalized lipophilic cations (DLC). DLC attachments to known bioactive compounds can direct organelle localization and improve drug exposure to targets within the mitochondria. Due to the mitochondria’s essential function and its regulation of cell death, DLC targeted therapies are the focus of drug discovery projects altering cellular fate via mitochondrial targets. This review provides an update on recent developments for the two main applications of DLCs: cytoprotective therapies aimed at reducing oxidative stress and cytotoxic therapies aimed at initiating cell death for the treatment of various cancers. Both approaches have produced significant improvements using DLC conjugated compounds that include improved potency, pharmacokinetic properties, and the potential to overcome resistance mechanisms.
Keywords: Anticancer, Cytotoxicity, Delocalized lipophilic cations, Mitochondria-targeted delivery, Oxidative stress, Smallmolecule drug design, Triphenylphosphonium.
Current Topics in Medicinal Chemistry
Title:Membrane Permeable Lipophilic Cations as Mitochondrial Directing Groups
Volume: 15 Issue: 8
Author(s): Joseph T. Madak and Nouri Neamati
Affiliation:
Keywords: Anticancer, Cytotoxicity, Delocalized lipophilic cations, Mitochondria-targeted delivery, Oxidative stress, Smallmolecule drug design, Triphenylphosphonium.
Abstract: The mitochondrion’s negatively charged membrane potential has been well documented to drive the accumulation of membrane permeable delocalized lipophilic cations (DLC). DLC attachments to known bioactive compounds can direct organelle localization and improve drug exposure to targets within the mitochondria. Due to the mitochondria’s essential function and its regulation of cell death, DLC targeted therapies are the focus of drug discovery projects altering cellular fate via mitochondrial targets. This review provides an update on recent developments for the two main applications of DLCs: cytoprotective therapies aimed at reducing oxidative stress and cytotoxic therapies aimed at initiating cell death for the treatment of various cancers. Both approaches have produced significant improvements using DLC conjugated compounds that include improved potency, pharmacokinetic properties, and the potential to overcome resistance mechanisms.
Export Options
About this article
Cite this article as:
Madak T. Joseph and Neamati Nouri, Membrane Permeable Lipophilic Cations as Mitochondrial Directing Groups, Current Topics in Medicinal Chemistry 2015; 15 (8) . https://dx.doi.org/10.2174/1568026615666150302105622
DOI https://dx.doi.org/10.2174/1568026615666150302105622 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Toxicology of Trastuzumab: An Insight into Mechanisms of Cardiotoxicity
Current Cancer Drug Targets Infants and Children with Tachycardia: Natural History and Drug Administration
Current Pharmaceutical Design Clinical Characteristics and Treatment of Cardiomyopathies in Children
Current Cardiology Reviews Endothelial Expression of MHC Class II Molecules in Autoimmune Disease
Current Pharmaceutical Design Endothelin-1 and Endothelin Converting Enzyme-1 in Human Atherosclerosis - Novel Targets for Pharmacotherapy in Atherosclerosis
Current Vascular Pharmacology Longevity Pathways (mTOR, SIRT, Insulin/IGF-1) as Key Modulatory Targets on Aging and Neurodegeneration
Current Topics in Medicinal Chemistry Obesity, Diabetes and Atrial Fibrillation; Epidemiology, Mechanisms and Interventions
Current Cardiology Reviews Role of AMPK in Diabetic Cardiovascular Complications: An Overview
Cardiovascular & Hematological Disorders-Drug Targets Biological Therapies: Effects of Proinflammatory Pathways and their Inhibition on the Myocardium of Rheumatoid Athritis Patients
Current Medicinal Chemistry Determinants of Left Ventricular Hypertrophy
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) The Role of Oxidative Stress in Smoking-Related Diseases
Mini-Reviews in Organic Chemistry Pharmacotherapy in Neonatal and Pediatric Extracorporeal Membrane Oxygenation (ECMO)
Current Drug Metabolism Effect of Simvastatin use on Autonomic Function in Patients with End Stage Renal Disease
Cardiovascular & Hematological Disorders-Drug Targets The FDG-PET Revolution of Medical Imaging – Four Decades and Beyond
Current Molecular Imaging (Discontinued) Cardiac Telocytes
Current Stem Cell Research & Therapy Investigational Positive Inotropic Agents for Acute Heart Failure
Cardiovascular & Hematological Disorders-Drug Targets p38 Mitogen-Activated Protein Kinase: A Critical Node Linking Insulin Resistance and Cardiovascular Diseases in Type 2 Diabetes Mellitus
Endocrine, Metabolic & Immune Disorders - Drug Targets Bone Marrow Stem Cell Therapy for Myocardial Angiogenesis
Current Vascular Pharmacology Electrochemical-Based Biosensors: New Diagnosis Platforms for Cardiovascular Disease
Current Medicinal Chemistry Pharmacogenomic Approaches for Tailored Anti-Leukemic Therapy in Children
Current Medicinal Chemistry