Exploring Scaffold Hopping for Novel 2-(Quinolin-4-yloxy)acetamides with Enhanced Antimycobacterial Activity.

ABSTRACT: Utilizing a scaffold-hopping strategy from the drug candidate telacebec, a novel series of 2-(quinolin-4-yloxy)acetamides was synthesized and evaluated as inhibitors of Mycobacterium tuberculosis (Mtb) growth. These compounds demonstrated potent activity against drug-sensitive and multidrug-resistant strains (MIC ≤ 0.02 μM). Leading compounds were evaluated against a known qcrB resistant strain (T313A), and their loss in activity suggested that the cytochrome bc₁ complex is the likely target. Additionally, these structures showed high selectivity regarding mammalian cells (selectivity index > 500) and stability across different aqueous media. Furthermore, some of the synthesized quinolines demonstrated aqueous solubility values that exceeded those of telaceb

SUBMITTER: Borsoi AF 

PROVIDER: S-EPMC11017393 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature