Abstract
New antituberculosis (anti-TB) drugs are urgently needed to battle drug-resistant Mycobacterium tuberculosis (Mtb) strains and to shorten the long treatment regimen. A series of isoxazole-based compounds, bearing a carboxy moiety at the C3 position, are highly potent and versatile anti-TB agents. Several members of this compound class exhibit submicromolar in vitro activity against replicating Mtb (R-TB) and thus comparable activity to the current first-line anti-TB drugs. Remarkably, certain compounds also show low micromolar activity in a model for nonreplicating Mtb (NRP-TB) phenotype, which is considered a key to shortening the current long treatment protocol. The series shows excellent selectivity towards Mtb and, in general, shows no cytotoxicity on Vero cells (IC50’s > 128 μM). Selected compounds retain their activity against isoniazid (INH), rifampin (RMP), and streptomycin (SM) resistant Mtb strains. The foregoing facts make derivatives of 3- isoxazolecarboxylic acid esters a promising anti-TB chemotype, and as such present attractive lead compounds for TB drug development.
Keywords: Isoxazole, Tuberculosis, mycobacterium, inhibition, drug-resistance, persistence, quinoline, micromolar activity, Vero cells, isoniazid (INH), rifampin (RMP), anti-TB chemotype, 3-isoxazolecarboxylic acid, Mefloquine
Current Topics in Medicinal Chemistry
Title:Derivatives of 3-Isoxazolecarboxylic Acid Esters - A Potent and Selective Compound Class against Replicating and Nonreplicating Mycobacterium tuberculosis
Volume: 12 Issue: 7
Author(s): Annamaria Lilienkampf, Marco Pieroni, Scott G. Franzblau, William R. Bishai and Alan P. Kozikowski
Affiliation:
Keywords: Isoxazole, Tuberculosis, mycobacterium, inhibition, drug-resistance, persistence, quinoline, micromolar activity, Vero cells, isoniazid (INH), rifampin (RMP), anti-TB chemotype, 3-isoxazolecarboxylic acid, Mefloquine
Abstract: New antituberculosis (anti-TB) drugs are urgently needed to battle drug-resistant Mycobacterium tuberculosis (Mtb) strains and to shorten the long treatment regimen. A series of isoxazole-based compounds, bearing a carboxy moiety at the C3 position, are highly potent and versatile anti-TB agents. Several members of this compound class exhibit submicromolar in vitro activity against replicating Mtb (R-TB) and thus comparable activity to the current first-line anti-TB drugs. Remarkably, certain compounds also show low micromolar activity in a model for nonreplicating Mtb (NRP-TB) phenotype, which is considered a key to shortening the current long treatment protocol. The series shows excellent selectivity towards Mtb and, in general, shows no cytotoxicity on Vero cells (IC50’s > 128 μM). Selected compounds retain their activity against isoniazid (INH), rifampin (RMP), and streptomycin (SM) resistant Mtb strains. The foregoing facts make derivatives of 3- isoxazolecarboxylic acid esters a promising anti-TB chemotype, and as such present attractive lead compounds for TB drug development.
Export Options
About this article
Cite this article as:
Lilienkampf Annamaria, Pieroni Marco, G. Franzblau Scott, R. Bishai William and P. Kozikowski Alan, Derivatives of 3-Isoxazolecarboxylic Acid Esters - A Potent and Selective Compound Class against Replicating and Nonreplicating Mycobacterium tuberculosis, Current Topics in Medicinal Chemistry 2012; 12 (7) . https://dx.doi.org/10.2174/156802612799984544
DOI https://dx.doi.org/10.2174/156802612799984544 |
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
-
Genome-wide Core Proteome Analysis of Brucella melitensis Strains for Potential Drug Target Prediction
Mini-Reviews in Medicinal Chemistry The Role of Coagulation and Fibrinolysis in the Pathogenesis of Acute Lung Injury
Current Respiratory Medicine Reviews Recent Progress in Biological Activities of Indole and Indole Alkaloids
Mini-Reviews in Medicinal Chemistry Thalidomide and Analogs as Anti-Inflammatory and Immunomodulator Drug Candidates
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Fused Aryl-Phenazines: Scaffold for the Development of Bioactive Molecules
Current Drug Targets Mycobacterium tuberculosis and Dendritic Cells: Whos Manipulating Whom?
Current Immunology Reviews (Discontinued) Prevalence of Tuberculosis in a Prison in Tehran by Active Case Finding
Infectious Disorders - Drug Targets Deciphering the Antimicrobial Activity of Phenanthroline Chelators
Current Medicinal Chemistry Targeting Folate Metabolism in the Human Malaria Parasite Plasmodium falciparum
Current Enzyme Inhibition Investigating Human P450s Involved in Drug Metabolism via Homology with High-Resolution P450 Crystal Structures of the CYP2C Subfamily
Current Drug Metabolism Obesity and the Aging Respiratory System
Current Respiratory Medicine Reviews The Gut Microbiota in Inflammatory Bowel Disease
Current Pharmaceutical Design Isoniazid Induced Convulsions at Therapeutic Dose in an Alcoholic and Smoker Patient
Current Drug Safety Oxidative Stress in the Molecular Mechanism of Pathogenesis at Different Diseased States of Organism in Clinics and Experiment
Current Drug Targets - Inflammation & Allergy Synthesis of Marine Natural Products with Antimalarial Activity
Mini-Reviews in Medicinal Chemistry Effect on Serum Uric Acid Levels of Drugs Prescribed for Indications other than Treating Hyperuricaemia
Current Pharmaceutical Design Medicinal and Beneficial Health Applications of Tinospora cordifolia (Guduchi): A Miraculous Herb Countering Various Diseases/Disorders and its Immunomodulatory Effects
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Recent Progress Towards the Identification of Inhibitors of Mycobacterial Cell Wall Polysaccharide Biosynthesis
Mini-Reviews in Medicinal Chemistry Predicting Antimicrobial Drugs and Targets with the MARCH-INSIDE Approach
Current Topics in Medicinal Chemistry Protective Mechanisms of Helminths Against Reactive Oxygen Species are Highly Promising Drug Targets
Current Medicinal Chemistry