Pyrido[1,2-a]benzimidazole-based agents active against tuberculosis (TB), multidrug-resistant (MDR) TB and extensively drug-resistant (XDR) TB.
The struggle against tuberculosis (TB) is still far from over. TB, caused by Mycobacterium tuberculosis, is one of the deadliest infections worldwide. Co-infection with human immunodeficiency virus (HIV) and the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains have further increased the burden for this disease. Herein, we report the discovery of 2-(4-chlorobenzyl)-3-methyl-1-oxo-1H,5H-pyrido[1,2-a]benzimidazole-4-carbonitrile as an effective antitubercular agent and the structural modifications of this molecule that have led to analogues with improved potency and lower toxicity. A number of these derivatives were also active at sub-micromolar concentrations against resistant TB strains and devoid of apparent toxicity to Vero cells, thereby underscoring their value as novel scaffolds for the development of new anti-TB drugs.
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood St., Chicago, IL 60612, USA.
Marco
M
Pieroni
Suresh K
SK
Tipparaju
Shichun
S
Lun
Yang
Y
Song
A Willem
AW
Sturm
William R
WR
Bishai
Alan P
AP
Kozikowski
D000995:Antitubercular Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004352:Drug Resistance, Microbial; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects*
D000995:Antitubercular Agents; D001562:Benzimidazoles
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