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
-
The Cardiovascular Nutrapharmacology of Resveratrol: Pharmacokinetics, Molecular Mechanisms and Therapeutic Potential
Current Medicinal Chemistry Scaffold Hopping for Identification of Novel PKCβII Inhibitors Based on Ligand and Structural Approaches, Virtual Screening and Molecular Dynamics Study
Combinatorial Chemistry & High Throughput Screening Animal Models Used for the Evaluation of Antiretroviral Therapies
Current HIV Research Takotsubo Cardiomyopathy: What we have Learned in the Last 25 Years? (A Comparative Literature Review)
Current Cardiology Reviews Pharmacological Targeting in Inherited Arrhythmia Syndromes
Current Medicinal Chemistry Perioperative Management of Intracranial Aneurysm and Subarachnoid Hemorrhage
Current Pharmaceutical Design Impact of Angiotensin Converting Enzyme Inhibitors/Angiotensin Receptors Blockers on Mortality in Acute Heart Failure Patients with Left Ventricular Systolic Dysfunction in the Middle East: Observations from the Gulf Acute Heart Failure Registry (Gulf CARE)
Current Vascular Pharmacology Toll-Like Receptors and Myocardial Ischemia/Reperfusion, Inflammation, and Injury
Current Cardiology Reviews Phytocompounds as Potential Agents to Treat Obesity-Cardiovascular Ailments
Cardiovascular & Hematological Agents in Medicinal Chemistry Recreational Drug Misuse and Stroke
Current Drug Abuse Reviews Ethanol and Inflammation
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Toll Like Receptors Signaling Pathways as a Target for Therapeutic Interventions
Current Signal Transduction Therapy Thioredoxin-1 is a Novel and Attractive Therapeutic Approach for Various Diseases Including Cardiovascular Disorders
Cardiovascular & Hematological Disorders-Drug Targets Pleiotropic Effects of Statin in Therapy in Heart Failure: A Review
Current Vascular Pharmacology Cardiovascular Drugs Inducing QT Prolongation: Facts and Evidence
Current Drug Safety Angiotensin Receptor Blockers in Chronic Heart Failure: Clinical Implications and Molecular Mechanisms
Current Cardiology Reviews Coinhibitory Molecule PD-1 as a Therapeutic Target in the Microenvironment of Multiple Myeloma
Current Cancer Drug Targets DNA Topoisomerase II Enzymes as Molecular Targets for Cancer Chemotherapy
Current Cancer Drug Targets The Multiple Roles of Vitamin D in Human Health. A Mini-Review
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Do You See What I See: Recognition of Protozoan Parasites by Toll-Like Receptors
Current Immunology Reviews (Discontinued)