Abstract
Chemotherapy is the primary means of treating protozoan parasitic infections. A problem for chemotherapy is to find a novel and potential molecule in protozoa, which could be exploited as drug target. To reach this goal, mitochondrion of protozoa can be considered as the most valuable and potential organelle because of its unique structure and function compared to their natural host habitat. In fact, the respiratory systems of parasitic protozoa typically show greater diversity in electron pathways than do their host animals. These unique aspects of electron transport chain (ETC) complexes and their related enzymes represent promising targets for chemotherapy. A cytochrome independent Alternative Oxidase (AOX) in parasites is a leading drug target. Topoisomerases play key functions in replication and organization of kDNA, which is present in a specialized region of unique mitochondria known as kinetoplast. They are considered as potential targets for anti-parasitic drugs. Moreover, a novel pathway of type II Fatty acid synthesis in mitochondria of trypanosomatids provides a new array of inhibitors that could be effective against these parasites. Recent studies on the emergence of drug resistance severely limit the arsenal of available drugs against protozoan parasites. Particularly, mutations of cytochrome b gene of ETC or changes in iron homeostasis by mitochondrial enzyme aconitase alter sensitivity of MDR1 and regulate resistance level to anti-parasitic drugs. This review summarizes recent state of our knowledge and understanding of the action of various therapeutically applied substances on mitochondria and their potential application in the future.
Keywords: Mitochondria, protozoa, electron transport chain, fatty acid synthesis, alternative oxidase, topoisomerase, drug resistance, apoptosis
Current Pharmaceutical Design
Title: Mitochondrion of Protozoan Parasite Emerges as Potent Therapeutic Target:Exciting Drugs are on the Horizon
Volume: 14 Issue: 9
Author(s): Nilkantha Sen and Hemanta K. Majumder
Affiliation:
Keywords: Mitochondria, protozoa, electron transport chain, fatty acid synthesis, alternative oxidase, topoisomerase, drug resistance, apoptosis
Abstract: Chemotherapy is the primary means of treating protozoan parasitic infections. A problem for chemotherapy is to find a novel and potential molecule in protozoa, which could be exploited as drug target. To reach this goal, mitochondrion of protozoa can be considered as the most valuable and potential organelle because of its unique structure and function compared to their natural host habitat. In fact, the respiratory systems of parasitic protozoa typically show greater diversity in electron pathways than do their host animals. These unique aspects of electron transport chain (ETC) complexes and their related enzymes represent promising targets for chemotherapy. A cytochrome independent Alternative Oxidase (AOX) in parasites is a leading drug target. Topoisomerases play key functions in replication and organization of kDNA, which is present in a specialized region of unique mitochondria known as kinetoplast. They are considered as potential targets for anti-parasitic drugs. Moreover, a novel pathway of type II Fatty acid synthesis in mitochondria of trypanosomatids provides a new array of inhibitors that could be effective against these parasites. Recent studies on the emergence of drug resistance severely limit the arsenal of available drugs against protozoan parasites. Particularly, mutations of cytochrome b gene of ETC or changes in iron homeostasis by mitochondrial enzyme aconitase alter sensitivity of MDR1 and regulate resistance level to anti-parasitic drugs. This review summarizes recent state of our knowledge and understanding of the action of various therapeutically applied substances on mitochondria and their potential application in the future.
Export Options
About this article
Cite this article as:
Sen Nilkantha and Majumder K. Hemanta, Mitochondrion of Protozoan Parasite Emerges as Potent Therapeutic Target:Exciting Drugs are on the Horizon, Current Pharmaceutical Design 2008; 14 (9) . https://dx.doi.org/10.2174/138161208784041024
DOI https://dx.doi.org/10.2174/138161208784041024 |
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
-
Advances in Analyses of Profens in Biological and Environmental Samples by Liquid Chromatography
Current Pharmaceutical Analysis Improvement in Quality of Life in Old People with Aortic Stenosis after Transcatheter Aortic Valve Implantation
Current Signal Transduction Therapy Can microRNAs be Biomarkers or Targets for Therapy of Ischemic Coronary Artery Disease in Metabolic Syndrome?
Current Drug Targets Lipid-Lowering Therapies for Atherosclerosis: Statins, Fibrates, Ezetimibe and PCSK9 Monoclonal Antibodies
Current Medicinal Chemistry FOXO and FOXM1 in Cancer: The FOXO-FOXM1 Axis Shapes the Outcome of Cancer Chemotherapy
Current Drug Targets Targeting ADAM12 in Human Disease: Head, Body or Tail?
Current Pharmaceutical Design Anti-Cancer Drugs Targeting Fatty Acid Synthase (FAS)
Recent Patents on Anti-Cancer Drug Discovery Pharmaceutical Measures to Prevent Doxorubicin-Induced Cardiotoxicity
Mini-Reviews in Medicinal Chemistry Oxidative/Nitrosative Stress and Immuno-inflammatory Pathways in Depression: Treatment Implications
Current Pharmaceutical Design Acute Respiratory Distress Syndrome-Past, Present and Future
Current Respiratory Medicine Reviews Cardiovascular Disease in Patients with Diabetic Nephropathy
Current Molecular Medicine Urine IL-18 is a Biomarker of Early Acute Kidney Injury (AKI)
Recent Patents on Biomarkers Infants and Children with Tachycardia: Natural History and Drug Administration
Current Pharmaceutical Design Role of Aberrant Lipid Metabolism of Cancer Stem Cells in Cancer Progression
Current Cancer Drug Targets Midkine: A Promising Molecule for Drug Development to Treat Diseases of the Central Nervous System
Current Pharmaceutical Design Antioxidative Effects of Rhodiola Genus: Phytochemistry and Pharmacological Mechanisms against the Diseases
Current Topics in Medicinal Chemistry Atrial Fibrillation and Ventricular Tachyarrhythmias: Advancements for Better Outcomes
Cardiovascular & Hematological Disorders-Drug Targets Lung Ultrasound in the Management of Acute Decompensated Heart Failure
Current Cardiology Reviews The Involvement of TNF-α in Cognitive Dysfunction Associated with Major Depressive Disorder: An Opportunity for Domain Specific Treatments
Current Neuropharmacology Role of Secondary Alcohol Metabolites in Anthracycline Cardiotoxicity: from Hypotheses to New Drugs
Drug Design Reviews - Online (Discontinued)