| Autor: |
Shirude PS; Department of Medicinal Chemistry, AstraZeneca India Pvt. Ltd., Bellary Road, Hebbal, Bangalore 560024, India. pravin.shirude@astrazeneca.com, Madhavapeddi P, Tucker JA, Murugan K, Patil V, Basavarajappa H, Raichurkar AV, Humnabadkar V, Hussein S, Sharma S, Ramya VK, Narayan CB, Balganesh TS, Sambandamurthy VK |
| Jazyk: |
angličtina |
| Zdroj: |
ACS chemical biology [ACS Chem Biol] 2013 Mar 15; Vol. 8 (3), pp. 519-23. Date of Electronic Publication: 2012 Dec 31. |
| DOI: |
10.1021/cb300510w |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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