Abstract
Thirty four novel 7-fluoro/nitro-1,2-dihydro-5-oxo-8-(sub)-5H-thiazolo[3,2-a]quinoline-4-carboxylic acids were synthesized from 2,4-dichlorobenzoic acid and 2,4-dichloro-5-fluoroacetophenone by multi step reaction, evaluated for in vitro and in vivo antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB) and Mycobacterium smegmatis (MC2) and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from M. smegmatis. Among the synthesized compounds, 8-[6-[[(1,1- dimethylethoxy)carbonyl]amino]-3-azabicyclo[3.1.0]hex-3-yl]-1,2-dihydro-7-nitro-5-oxo-5H-thiazolo[3,2-a]quinoline-4- carboxylic acid (10q) was found to be the most active compound in vitro with MIC of 0.08 μM and < 0.08 μM against MTB and MDR-TB respectively. Compound 10q was found to be 4.5 and > 570 times more potent than isoniazid against MTB and MDR-TB respectively. In the in vivo animal model 10q decreased the bacterial load in lung and spleen tissues with 2.51 and 3.71-log10 protections respectively at the dose of 50 mg/kg body weight.
Keywords: Antimycobacterial activity, antitubercular activity, tuberculosis, thiazoloquinolone
Medicinal Chemistry
Title: Synthesis, Antimycobacterial Activities and Phototoxic Evaluation of 5H-thiazolo[3,2-a]quinoline-4-carboxylic Acid Derivatives
Volume: 4 Issue: 5
Author(s): Murugesan Dinakaran, Palaniappan Senthilkumar, Perumal Yogeeswari, Arnab China, Valakunja Nagaraja and Dharmarajan Sriram
Affiliation:
Keywords: Antimycobacterial activity, antitubercular activity, tuberculosis, thiazoloquinolone
Abstract: Thirty four novel 7-fluoro/nitro-1,2-dihydro-5-oxo-8-(sub)-5H-thiazolo[3,2-a]quinoline-4-carboxylic acids were synthesized from 2,4-dichlorobenzoic acid and 2,4-dichloro-5-fluoroacetophenone by multi step reaction, evaluated for in vitro and in vivo antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB) and Mycobacterium smegmatis (MC2) and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from M. smegmatis. Among the synthesized compounds, 8-[6-[[(1,1- dimethylethoxy)carbonyl]amino]-3-azabicyclo[3.1.0]hex-3-yl]-1,2-dihydro-7-nitro-5-oxo-5H-thiazolo[3,2-a]quinoline-4- carboxylic acid (10q) was found to be the most active compound in vitro with MIC of 0.08 μM and < 0.08 μM against MTB and MDR-TB respectively. Compound 10q was found to be 4.5 and > 570 times more potent than isoniazid against MTB and MDR-TB respectively. In the in vivo animal model 10q decreased the bacterial load in lung and spleen tissues with 2.51 and 3.71-log10 protections respectively at the dose of 50 mg/kg body weight.
Export Options
About this article
Cite this article as:
Dinakaran Murugesan, Senthilkumar Palaniappan, Yogeeswari Perumal, China Arnab, Nagaraja Valakunja and Sriram Dharmarajan, Synthesis, Antimycobacterial Activities and Phototoxic Evaluation of 5H-thiazolo[3,2-a]quinoline-4-carboxylic Acid Derivatives, Medicinal Chemistry 2008; 4 (5) . https://dx.doi.org/10.2174/157340608785700225
DOI https://dx.doi.org/10.2174/157340608785700225 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...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
-
Therapeutic Modulation of Cytokines in Chronic Infectious Diseases
Current Pharmaceutical Design Patent Selections
Recent Patents on DNA & Gene Sequences Crucial Enzymes in the Hydroxylated Triacylglycerol-ricinoleate Biosynthesis Pathway of Castor Bean
Current Protein & Peptide Science Noninvasive Assessment of Cytokines in Occupational Respiratory Diseases
Recent Patents on Inflammation & Allergy Drug Discovery Current Study of Medicinal Chemistry for Treating Spinal Tuberculosis
Current Medicinal Chemistry Peptide Biomarkers: Exploring the Diagnostic Aspect
Current Protein & Peptide Science Newer Insights in Personalized and Evidence Based Medicine- the Role of MicroRNAs
Current Pharmacogenomics and Personalized Medicine Genomic and Genetic Approaches for the Identification of Antifungal Drug Targets
Infectious Disorders - Drug Targets Pleiotropic Regulatory Genes as A Tool for <i>Streptomyces</i> Strains Bioprospecting and Improvement
Current Biotechnology Mass Spectrometry-Based Proteomics and its Application to Studies of Porphyromonas gingivalis Invasion and Pathogenicity
Infectious Disorders - Drug Targets Synthetic and Medicinal Prospective of Structurally Modified Curcumins
Current Topics in Medicinal Chemistry Hybrid Bioactive Heterocycles as Potential Antimicrobial Agents: A Review
Mini-Reviews in Medicinal Chemistry Prevalence of Tuberculosis in a Prison in Tehran by Active Case Finding
Infectious Disorders - Drug Targets Improvements in Algorithms for Phenotype Inference: The NAT2 Example
Current Drug Metabolism Chaperone-like Activity of alpha-Crystallin and Other Small Heat Shock Proteins
Current Protein & Peptide Science Targeting the Folate Receptor: Improving Efficacy in Inorganic Medicinal Chemistry
Current Medicinal Chemistry Reactive Oxygen Species in the Initiation of IL-4 Driven Autoimmunity as a Potential Therapeutic Target
Current Pharmaceutical Design Anticancer Drug Discovery Targeting DNA Hypermethylation
Current Medicinal Chemistry Renal & Ocular Targets for Therapy in Wegeners Granulomatosis
Inflammation & Allergy - Drug Targets (Discontinued) Tumour Mutation Profiling with High-throughput Multiplexed Genotyping: A Review of its Use for Guiding Targeted Cancer Therapy
Current Cancer Therapy Reviews