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
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
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
- 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
-
Vitamin D/VDR in Acute Kidney Injury: A Potential Therapeutic Target
Current Medicinal Chemistry Biomarkers Associated with Bleeding Risk in the Setting of Atrial Fibrillation
Current Medicinal Chemistry Gene Transfer for Inherited Metabolic Disorders of the Liver: Immunological Challenges
Current Pharmaceutical Design Oxidative Stress and Drugs of Abuse: An Update
Mini-Reviews in Organic Chemistry Non-Alcoholic Steatohepatitis: What Can We Learn from Animal Models?
Current Medicinal Chemistry Propranolol Safety Profile in Children
Current Drug Safety Cytoprotection by Natural and Synthetic Polyphenols in the Heart: Novel Mechanisms and Perspectives
Current Pharmaceutical Design Targeting MDM4 as a Novel Therapeutic Approach for Hematologic Malignancies
Current Cancer Drug Targets Autophagy Inhibition Rescues Against Leptin-Induced Cardiac Contractile Dysfunction
Current Pharmaceutical Design Treatment of Chronic Hepatitis C Virus Using Direct Acting Antivirals in Geriatric Egyptian Patients
Recent Advances in Anti-Infective Drug Discovery Recent Updates on Current and Upcoming Biomarkers for Cardiovascular Diseases
Current Pharmaceutical Design EDITORIAL [Hot Topic: Transthyretin: A Small Protein in the Big World of Amyloidoses (Guest Editors: Adriano Martinelli and Gabriella Ortore)]
Current Medicinal Chemistry Patent Selections :
Recent Patents on Cardiovascular Drug Discovery Inotropic and Vasoactive Drugs in Pediatric ICU
Current Drug Targets Altered Prolylcarboxypeptidase Expression and Function in Response to Different Risk Factors of Diabetes
Cardiovascular & Hematological Agents in Medicinal Chemistry Transthyretin Deposition in Familial Amyloidotic Polyneuropathy
Current Medicinal Chemistry Prevention of Left Ventricular Remodelling after Acute Myocardial Infarction: An Update
Recent Patents on Cardiovascular Drug Discovery Free Radicals and Antioxidants: How to Reestablish Redox Homeostasis in Chronic Diseases?
Current Medicinal Chemistry Stem Cell Based Preclinical Drug Development and Toxicity Prediction
Current Pharmaceutical Design Stem Cells as a Novel Tool for Drug Screening and Treatment of Degenerative Diseases
Current Pharmaceutical Design