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Eur J Med Chem ; 123: 557-567, 2016 Nov 10.
Article in English | MEDLINE | ID: mdl-27517804

ABSTRACT

The dual effect of FtsZ inhibition and oxidative stress by a group of 1,2-dihydroquinolines that culminate in bactericidal effect on mycobacterium strains is demonstrated. They inhibited the non-pathogenic Mycobacterium smegmatis mc(2) 155 with MIC as low as 0.9 µg/mL and induced filamentation. Detailed studies revealed their ability to inhibit polymerization and GTPase activity of MtbFtsZ (Mycobacterial filamentous temperature sensitive Z) with an IC50 value of ∼40 µM. In addition to such target specific effects, these compounds exerted a global cellular effect by causing redox-imbalance that was evident from overproduction of ROS in treated cells. Such multi-targeting effect with one chemical scaffold has considerable significance in this era of emerging drug resistance and could offer promise in the development of new therapeutic agents against tuberculosis.


Subject(s)
Bacterial Proteins/antagonists & inhibitors , Mycobacterium smegmatis/drug effects , Mycobacterium smegmatis/metabolism , Quinones/chemistry , Quinones/pharmacology , Bacillus subtilis/drug effects , GTP Phosphohydrolases/chemistry , Microbial Sensitivity Tests , Oxidation-Reduction/drug effects , Protein Multimerization/drug effects , Protein Structure, Quaternary , Reactive Oxygen Species/metabolism
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