Document Detail

Structure-activity relationships for a series of quinoline-based compounds active against replicating and nonreplicating Mycobacterium tuberculosis.
MedLine Citation:
PMID:  19271749     Owner:  NLM     Status:  MEDLINE    
Tuberculosis (TB) remains as a global pandemic that is aggravated by a lack of health care, the spread of HIV, and the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains. New anti-TB drugs are urgently required to shorten the long 6-12 month treatment regimen and to battle drug-resistant Mtb strains. We have identified several potent quinoline-based anti-TB compounds, bearing an isoxazole containing side-chain. The most potent compounds, 7g and 13, exhibited submicromolar activity against the replicating bacteria (R-TB), with minimum inhibitory concentrations (MICs) of 0.77 and 0.95 microM, respectively. In general, these compounds also had micromolar activity against the nonreplicating persistent bacteria (NRP-TB) and did not show toxicity on Vero cells up to 128 microM concentration. Compounds 7g and 13 were shown to retain their anti-TB activity against rifampin, isoniazid, and streptomycin resistant Mtb strains. The results suggest that quinoline-isoxazole-based anti-TB compounds are promising leads for new TB drug development.
Annamaria Lilienkampf; Jialin Mao; Baojie Wan; Yuehong Wang; Scott G Franzblau; Alan P Kozikowski
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  52     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-02     Completed Date:  2009-04-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2109-18     Citation Subset:  IM    
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
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MeSH Terms
Antitubercular Agents / chemical synthesis*,  chemistry,  pharmacology
Cercopithecus aethiops
Drug Resistance, Bacterial*
Drug Resistance, Multiple, Bacterial
Isoxazoles / chemical synthesis*,  chemistry,  pharmacology
Microbial Sensitivity Tests
Mycobacterium tuberculosis / drug effects*,  physiology
Quinolines / chemical synthesis*,  chemistry,  pharmacology
Structure-Activity Relationship
Vero Cells
Reg. No./Substance:
0/Antitubercular Agents; 0/Isoxazoles; 0/Quinolines

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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