9 research outputs found
Assessment of areca nut use, practice and dependency among people in Guwahati, Assam:A cross-sectional study
Cigarettes and Other Tobacco Products Act (COTPA) implementation in education institutions in India:A crosssectional study
Assessment of knowledge and screening in oral, breast, and cervical cancer in the population of the Northeast region of India
The role of frontline community health workers in the non-communicable disease screening program in Assam, India:Current trends, challenges and scope - A time and motion study
Oncology-Based Palliative Care Development:The approach, challenges, and solutions from north-east region of India, a model for low: The middle-income countries
Assessing Price Elasticity for Private Labels and National Brands: Differences by Income and Store Location
Discovery and Optimization of DNA Gyrase and Topoisomerase IV Inhibitors with Potent Activity against Fluoroquinolone-Resistant Gram-Positive Bacteria.
Herein, we describe the discovery and optimization of a novel series that inhibits bacterial DNA gyrase and topoisomerase IV via binding to, and stabilization of, DNA cleavage complexes. Optimization of this series led to the identification of compound 25, which has potent activity against Gram-positive bacteria, a favorable in vitro safety profile, and excellent in vivo pharmacokinetic properties. Compound 25 was found to be efficacious against fluoroquinolone-sensitive Staphylococcus aureus infection in a mouse thigh model at lower doses than moxifloxacin. An X-ray crystal structure of the ternary complex formed by topoisomerase IV from Klebsiella pneumoniae, compound 25, and cleaved DNA indicates that this compound does not engage in a water-metal ion bridge interaction and forms no direct contacts with residues in the quinolone resistance determining region (QRDR). This suggests a structural basis for the reduced impact of QRDR mutations on antibacterial activity of 25 compared to fluoroquinolones