Aminopyrazinamides: Novel and Specific GyrB Inhibitors that Kill Replicating and Nonreplicating Mycobacterium tuberculosis
ACS Chemical Biology2012Vol. 8(3), pp. 519–523
Citations Over TimeTop 10% of 2012 papers
Pravin S. Shirude, Prashanti Madhavapeddi, Julie A. Tucker, Kannan Murugan, Vikas Patil, Halesha D. Basavarajappa, Anandkumar Raichurkar, Vaishali Humnabadkar, Syeed Hussein, Sreevalli Sharma, V. K. Ramya, Chandan Narayan, Tanjore S. Balganesh, Vasan K. Sambandamurthy
Abstract
Aminopyrazinamides originated from a high throughput screen targeting the Mycobacterium smegmatis (Msm) GyrB ATPase. This series displays chemical tractability, robust structure-activity relationship, and potent antitubercular activity. The crystal structure of Msm GyrB in complex with one of the aminopyrazinamides revealed promising attributes of specificity against other broad spectrum pathogens and selectivity against eukaryotic kinases due to novel interactions at hydrophobic pocket, unlike other known GyrB inhibitors. The aminopyrazinamides display excellent mycobacterial kill under in vitro, intracellular, and hypoxic conditions.
Related Papers
- → Progression to Active Tuberculosis, but Not Transmission, Varies byMycobacterium tuberculosisLineage in The Gambia(2008)298 cited
- → Transcriptional signatures of Mycobacterium tuberculosis in mouse model of intraocular tuberculosis(2019)9 cited
- → Transcriptional Biomarkers of Differentially Detectable Mycobacterium tuberculosis in Patient Sputum(2022)9 cited
- → The wag31 gene of Mycobacterium tuberculosis is positively regulated by the stringent response(2011)7 cited
- [Establishment and drug susceptibility test of isoniazid resistant Mycobacterium smegmatis].(2011)