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 |
Call for Papers in Thematic Issues
Ayurvedic medicinal therapeutic approaches for inflammatory and neurodegenerative disorders
Usually, in our elderly population, neurodegenerative disorders occur due to neuron death. Alzheimer?s disease (AD) is an irreversible and progressive neurodegenerative disease. Dementia is the leading cause of AD, which affects about 30 million people worldwide. According to the World Alzheimer report 2018, a new case of dementia develops every ...read more
Recent Advances in Biotransformation of Bioactive Terpenoids using Aspergillus niger
Biotransformation is the reaction catalyzed by biological catalysts of either isolated enzymes or whole cell cultures of microorganisms. This process has been extensively applied in the conversion of bioactive terpenoids with high regio- and stereospecifity. This process has been also applied in the lead discovery and development. Aspergillus niger has ...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
Related Articles
-
Genomic Instability in Cancer: Molecular Mechanisms and Therapeutic Potentials
Current Pharmaceutical Design Stereoselective Synthesis and Antiproliferative Activity of Monoterpene-Fused 2- Imino-1,3-oxazines
Current Organic Synthesis Establishment of Conditionally Immortalized Cell Lines with Specific Functions and its Application to Differential Gene Expression Analysis by DNA Microarray Technology
Current Pharmaceutical Analysis The Physio-Pharmacological Role of the NPS/NPSR System in Psychiatric Disorders: A Translational Overview
Current Protein & Peptide Science Serum Insulin Degrading Enzyme Level and Other Factors in Type 2 Diabetic Patients with Mild Cognitive Impairment
Current Alzheimer Research A Fluorene based Fluorogenic ''Turn-off'' Chemosensor for the Recognition of Cu<sup>2+</sup> and Fe<sup>2+</sup>: Computational Modeling and Living-cell Application
Current Analytical Chemistry Synthesis and Biological Evaluation of Novel Chromone+Donepezil Hybrids for Alzheimer’s Disease Therapy
Current Alzheimer Research QSAR and Docking Studies on Propenone Derivatives as Dual COX and 5- LOX Inhibitors
Letters in Organic Chemistry Forced Abstinence Model of Relapse to Study Pharmacological Treatments of Substance Use Disorder
Current Drug Abuse Reviews [General Articles] Natriuretic Peptides in Alcohol Withdrawal: Central and Peripheral Mechanisms
Current Medicinal Chemistry Metabotropic Glutamate Receptors and Interacting Proteins in Epileptogenesis
Current Neuropharmacology Management of a Mental Health Crisis in an International High School Exchange Student: A Case Study
Adolescent Psychiatry Phytohormone Crosstalk Research: Cytokinin and its Crosstalk with Other Phytohormones
Current Protein & Peptide Science Adrenocortical Crisis Triggered by Levothyroxine in an Unrecognized Autoimmune Polyglandular Syndrome Type-2: A Case Report with Review of the Literature
Current Drug Safety Therapeutic Drugs that Behave as Mechanism-Based Inhibitors of Cytochrome P450 3A4
Current Drug Metabolism Computational Methods for De novo Protein Design and its Applications to the Human Immunodeficiency Virus 1, Purine Nucleoside Phosphorylase, Ubiquitin Specific Protease 7, and Histone Demethylases
Current Drug Targets A Tour of Unsupervised Deep Learning for Medical Image Analysis
Current Medical Imaging Meet Our Editorial Board Member:
Combinatorial Chemistry & High Throughput Screening Endocrine Therapy for Advanced Breast Cancer: Beyond Tamoxifen and Aromatase Inhibitors
Current Cancer Therapy Reviews Glycogen Synthase Kinase 3 (GSK3): Its Role and Inhibitors
Current Topics in Medicinal Chemistry