FtsZ inhibition and redox modulation with one chemical scaffold: Potential use of dihydroquinolines against mycobacteria
| Autor: | Sridevi Duggirala, V. Senu Adeeba, Muraleedharan K. Manheri, Mukesh Doble, John Victor Napoleon, Rakesh P. Nankar |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Mycobacterium smegmatis GTPase Microbial Sensitivity Tests medicine.disease_cause GTP Phosphohydrolases 03 medical and health sciences Filamentation Bacterial Proteins Drug Discovery medicine FtsZ Overproduction Protein Structure Quaternary IC50 Pharmacology biology Chemistry Organic Chemistry Quinones General Medicine biology.organism_classification 030104 developmental biology Biochemistry biology.protein Protein Multimerization Reactive Oxygen Species Oxidation-Reduction Oxidative stress Mycobacterium Bacillus subtilis |
| Zdroj: | European journal of medicinal chemistry. 123 |
| ISSN: | 1768-3254 |
| Popis: | 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 mc2 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect