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
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
-
<i>In silico</i> Modeling of Antimalarial Protein Kinase Inhibitors
Letters in Drug Design & Discovery SCYPPred: A Web-Based Predictor of SNPs for Human Cytochrome P450
Protein & Peptide Letters Prevalence of Dilated Cardiomyopathy in HIV-Infected African Patients Not Receiving HAART: A Multicenter, Observational, Prospective, Cohort Study in Rwanda
Current HIV Research Volatile Disease Biomarkers in Breath: A Critique
Current Pharmaceutical Biotechnology Asthma in Childhood – Making the Diagnosis
Current Pediatric Reviews Theoretical Modeling of HPV: QSAR and Novodesign with Fragment Approach
Current Computer-Aided Drug Design Rashes, Sniffles, and Stroke: A Role for Infection in Ischemic Stroke of Childhood
Infectious Disorders - Drug Targets Gene Therapy by Liver Transplantation and Single Stranded Oligonucleotides (SSOs) in Familial Amyloidotic Polyneuropathy (FAP)
Current Pharmacogenomics Regulation of Cytokine Production by γδ T Cells
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents A Brief Review of the Essential Role of Nanovehicles for Improving the Therapeutic Efficacy of Pharmacological Agents Against Tumours
Current Drug Delivery Current Approaches for New TB Drugs
Current Respiratory Medicine Reviews Proteome Analysis of Ofloxacin and Moxifloxacin Induced Mycobacterium tuberculosis Isolates by Proteomic Approach
Protein & Peptide Letters Subject Index to Volume 1
Letters in Drug Design & Discovery Glycoconjugates of Quinolines: Application in Medicinal Chemistry
Mini-Reviews in Medicinal Chemistry Clinical and Forensic Aspects of Pharmacobezoars
Current Drug Research Reviews Acute Appendicitis as a Manifestation of the Immune Reconstitution Inflammatory Syndrome
Current HIV Research Phylogenetic, Sequence Analysis and Structural Studies of Maturase K Proteins from Mangroves
Current Chemical Biology Simultaneously Determining Seven Second-Line Anti-TB Drugs by UHPLC- MS: Application for TDM in HIV-TB Patients
Current Pharmaceutical Analysis A High-Throughput Assay for Developing Inhibitors of PhoP, a Virulence Factor of Mycobacterium tuberculosis
Combinatorial Chemistry & High Throughput Screening Structure-based Discovery of Narirutin as a Shikimate kinase Inhibitor with Anti-tubercular Potency
Current Computer-Aided Drug Design