Abstract
Azoles have consistently been recognized as the mainstays of antifungal drugs, amongst which ergosterol prevails as an integral component of fungal plasma membrane. It is most commonly produced via demethylation of lanosterol by the cytochrome P450-dependent enzyme lanosterol 14α-demethylase. Azoles exert their antifungal activities via binding to lanosterol 14 α-demethylase and thereby preventing the demethylation of lanosterol. This leads to the depletion of demethylated lanosterol (ergosterol) with the concomitant accumulation of methylated sterol precursors (lanosterol, 4,14-dimethylzymosterol, and 24-methylenedihydrolanosterol) and deterioration of the membrane integrity, resulting in fungal growth inhibition. Resistance to azoles is a concern, particularly during the long-term treatment of fungus mediated cellular complications. To combat azole resistance and to extend the spectrum of treatable pathogens, the development of novel and more potent azoles, with alteration in active sites has attracted worldwide scientific attention. With such an insight, this review focuses on antifungal potentials of azole compounds with an emphasis on the corresponding drug resistance episodes complemented with novel strategies for the development of new generation of azole compounds.
Keywords: Azole, lanosterol, ergosterol, 14-α-lanosterol-demethylase, structure-function relationship, drug resistance.
The Natural Products Journal
Title:Relationship of Azole Resistance with the Structural Alteration of the Target Sites: Novel Synthetic Compounds for Better Antifungal Activities
Volume: 4 Issue: 2
Author(s): Parth Malik, Narender Chaudhry, Bheru S. Kitawat, Raman Kumar and Tapan K. Mukherjee
Affiliation:
Keywords: Azole, lanosterol, ergosterol, 14-α-lanosterol-demethylase, structure-function relationship, drug resistance.
Abstract: Azoles have consistently been recognized as the mainstays of antifungal drugs, amongst which ergosterol prevails as an integral component of fungal plasma membrane. It is most commonly produced via demethylation of lanosterol by the cytochrome P450-dependent enzyme lanosterol 14α-demethylase. Azoles exert their antifungal activities via binding to lanosterol 14 α-demethylase and thereby preventing the demethylation of lanosterol. This leads to the depletion of demethylated lanosterol (ergosterol) with the concomitant accumulation of methylated sterol precursors (lanosterol, 4,14-dimethylzymosterol, and 24-methylenedihydrolanosterol) and deterioration of the membrane integrity, resulting in fungal growth inhibition. Resistance to azoles is a concern, particularly during the long-term treatment of fungus mediated cellular complications. To combat azole resistance and to extend the spectrum of treatable pathogens, the development of novel and more potent azoles, with alteration in active sites has attracted worldwide scientific attention. With such an insight, this review focuses on antifungal potentials of azole compounds with an emphasis on the corresponding drug resistance episodes complemented with novel strategies for the development of new generation of azole compounds.
Export Options
About this article
Cite this article as:
Malik Parth, Chaudhry Narender, Kitawat S. Bheru, Kumar Raman and Mukherjee K. Tapan, Relationship of Azole Resistance with the Structural Alteration of the Target Sites: Novel Synthetic Compounds for Better Antifungal Activities, The Natural Products Journal 2014; 4 (2) . https://dx.doi.org/10.2174/221031550402141009100455
DOI https://dx.doi.org/10.2174/221031550402141009100455 |
Print ISSN 2210-3155 |
Publisher Name Bentham Science Publisher |
Online ISSN 2210-3163 |
- 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
Related Articles
-
Retromer Dysfunction and Neurodegenerative Disease
Current Genomics Conceptualizing Excessive Behaviour Syndromes: A Systematic Review
Current Psychiatry Reviews Synthesis of New Cyclic Imides Derived From Safrole, Structure- and Ligand-based Approaches to Evaluate Potential New Multitarget Agents Against Species of Leishmania
Medicinal Chemistry Genetic Risk Factors for Glaucoma and Exfoliation Syndrome Identified by Genome-wide Association Studies
Current Neuropharmacology Sex Steroids in Autoimmune Diseases
Current Topics in Medicinal Chemistry Lipoxygenase (LOX) Pathway: A Promising Target to Combat Cancer
Current Pharmaceutical Design Sex Hormones and Brain Dopamine Functions
Central Nervous System Agents in Medicinal Chemistry Interception of Cocaine by Enzyme or Antibody Delivered with Viral Gene Transfer: A Novel Strategy for Preventing Relapse in Recovering Drug Users
CNS & Neurological Disorders - Drug Targets Gene and Stem Cell Therapy in the Treatment of Erectile Dysfunction and Pulmonary Hypertension; Potential Treatments for the Common Problem of Endothelial Dysfunction
Current Gene Therapy A Role for Glutathione in the Pathophysiology of Bipolar Disorder and Schizophrenia? Animal Models and Relevance to Clinical Practice
Current Medicinal Chemistry Alpha-1 Antitrypsin Deficiency and Chronic Obstructive Pulmonary Disease: Between Overlaps, Phenotypes and Illnesses
Current Respiratory Medicine Reviews Sensory-Motor Integration in the Medial Medulla
Current Neuropharmacology Steroid 5α-Reductase as a Novel Therapeutic Target for Schizophrenia and Other Neuropsychiatric Disorders
Current Pharmaceutical Design Structure-Based Approaches in the Design of GSK-3 Selective Inhibitors
Current Protein & Peptide Science Antioxidant Properties of Hydroxycinnamic Acids: A Review of Structure- Activity Relationships
Current Medicinal Chemistry Meet Our Editorial Board Member
Current Alzheimer Research Current Problems, New Opportunities and Future Directions of Antiplatelet Therapy - Increasing Role of Novel Antiplatelet Agents in Cardiovascular Diseases
Recent Patents on Cardiovascular Drug Discovery Biological and Clinical Significance of Polymorphisms in NAD(P)H: Quinone Oxidoreductase 1 (NQO1)
Current Pharmacogenomics Meet Our Editorial Board Member
Current Psychiatry Reviews Challenging Treatment-Resistant Major Depressive Disorder: A Roadmap for Improved Therapeutics
Current Neuropharmacology