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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Pyrido[1,2-a]benzimidazole-Based Agents Active Against Tuberculosis (TB), Multidrug-Resistant (MDR) TB and Extensively Drug-Resistant (XDR) TB
ChemMedChem, Volume 6, No. 2, Year 2011
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Description
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. Waging war on TB: Using high-throughput screening, we have identified a pyrido[1,2-a]benzimidazole as a potent antitubercular agents. Chemical modifications to the hit compound led to an analogue (3h) with improved potency and reduced toxicity. Of considerable interest was the finding that 3h maintained activity against two extensively drug-resistant strains and one multidrug-resistant strain of tuberculosis (TB). These compounds represent promising leads in the quest for improved anti-TB drugs. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Authors & Co-Authors
Pieroni, Marco
United States, Chicago
University of Illinois at Chicago
Tipparaju, Suresh K.
United States, Chicago
University of Illinois at Chicago
Lun, Shichun
United States, Baltimore
Johns Hopkins School of Medicine
Song, Yang
United States, Chicago
University of Illinois at Chicago
Sturm, Adriaan Willem
South Africa, Durban
The Nelson R. Mandela Medical School
Bishai, William R.
United States, Baltimore
Johns Hopkins School of Medicine
Kozikowski, Alan P.
United States, Chicago
University of Illinois at Chicago
Statistics
Citations: 57
Authors: 7
Affiliations: 3
Identifiers
Doi:
10.1002/cmdc.201000490
ISSN:
18607179
e-ISSN:
18607187
Research Areas
Infectious Diseases