Efficacy and Improved Resistance Potential of a Cofactor-Independent InhA Inhibitor of Mycobacterium tuberculosis in the C3HeB/FeJ Mouse Model
| Autor: | Jason Halladay, Tanya Parish, Wai Choi, Vincent Hernandez, Anne J. Lenaerts, Anthony J. Smith, Matthew B. McNeil, Gregory T. Robertson, Victoria A. Ektnitphong, Michael S. Scherman, Pamela Berry, Weimin Mao, Aaron Korkegian, Devon Dennison, Yi Xia, Yasheen Zhou, David S. Carter, M. R. K. Alley |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Boron Compounds
isoniazid caseum Tuberculosis Hydrocarbons Fluorinated necrotic lesions Antitubercular Agents Microbial Sensitivity Tests Microbiology Mycobacterium tuberculosis Mice 03 medical and health sciences Antibiotic resistance Pharmacotherapy Drug Development Extracellular Animals Medicine Inhibins Experimental Therapeutics Pharmacology (medical) antimicrobial resistance C3HeB/FeJ mice Lung Tuberculosis Pulmonary 030304 developmental biology Pharmacology Aza Compounds Mice Inbred C3H 0303 health sciences biology 030306 microbiology business.industry INHA Isoniazid Editor's Pick biology.organism_classification medicine.disease Bacterial Load Disease Models Animal Infectious Diseases tuberculosis Drug development Female business medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.02071-18 |
| Popis: | AN12855 is a direct, cofactor-independent inhibitor of InhA in Mycobacterium tuberculosis. In the C3HeB/FeJ mouse model with caseous necrotic lung lesions, AN12855 proved efficacious with a significantly lower resistance frequency than isoniazid. AN12855 is a direct, cofactor-independent inhibitor of InhA in Mycobacterium tuberculosis. In the C3HeB/FeJ mouse model with caseous necrotic lung lesions, AN12855 proved efficacious with a significantly lower resistance frequency than isoniazid. AN12855 drug levels were better retained in necrotic lesions and caseum where the majority of hard to treat, extracellular bacilli reside. Owing to these combined attributes, AN12855 represents a promising alternative to the frontline antituberculosis agent isoniazid. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|