FtsZ inhibition and redox modulation with one chemical scaffold: Potential use of dihydroquinolines against mycobacteria

European Journal of Medicinal Chemistry
2016.0

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.

Knowledge Graph

Similar Paper

FtsZ inhibition and redox modulation with one chemical scaffold: Potential use of dihydroquinolines against mycobacteria
European Journal of Medicinal Chemistry 2016.0
Functionalized Dioxonaphthoimidazoliums: A Redox Cycling Chemotype with Potent Bactericidal Activities against Mycobacterium tuberculosis
Journal of Medicinal Chemistry 2021.0
2-(Quinolin-4-yloxy)acetamides Are Active against Drug-Susceptible and Drug-Resistant Mycobacterium tuberculosis Strains
ACS Medicinal Chemistry Letters 2016.0
The synthesis and evaluation of quinolinequinones as anti-mycobacterial agents
Bioorganic & Medicinal Chemistry 2019.0
1H-Benzo[d]imidazoles and 3,4-dihydroquinazolin-4-ones: Design, synthesis and antitubercular activity
European Journal of Medicinal Chemistry 2018.0
Antimycobacterial activities of novel 2-(sub)-3-fluoro/nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid
Bioorganic & Medicinal Chemistry 2008.0
Anti-tubercular activity of novel 4-anilinoquinolines and 4-anilinoquinazolines
Bioorganic & Medicinal Chemistry Letters 2019.0
Targeting FtsZ for Antituberculosis Drug Discovery:  Noncytotoxic Taxanes as Novel Antituberculosis Agents
Journal of Medicinal Chemistry 2006.0
Antibacterial activity of N -methylbenzofuro[3,2- b ]quinoline and N -methylbenzoindolo[3,2- b ]-quinoline derivatives and study of their mode of action
European Journal of Medicinal Chemistry 2017.0
Development of antitubercular compounds based on a 4-quinolylhydrazone scaffold. Further structure–activity relationship studies
Bioorganic & Medicinal Chemistry 2009.0