Ligand-Based Virtual Screening for Discovery of Indole Derivatives as Potent DNA Gyrase ATPase Inhibitors Active against and Hit Validation by Biological Assays.

is the single most important global infectious disease killer and a World Health Organization critical priority pathogen for development of new antimicrobials. DNA gyrase is a validated target for anti-TB agents, but those in current use target DNA breakage-reunion, rather than the ATPase activity of the GyrB subunit. Here, virtual screening, subsequently validated by whole-cell and enzyme inhibition assays, was applied to identify candidate compounds that inhibit GyrB ATPase activity from the Specs compound library.

Toward the early diagnosis of tuberculosis: A gold particle-decorated graphene-modified paper-based electrochemical biosensor for Hsp16.3 detection.

Tuberculosis (TB) currently remains a major life-threatening disease as it can be fatal if not treated properly or in a timely manner. Herein, we first describe a disposable and cost-effective paper-based electrochemical biosensor based on a gold particle-decorated carboxyl graphene (AuPs/GCOOH)-modified electrode for detecting heat shock protein (Hsp16.3), which is a specific biomarker indicating the onset of TB infection.

Bioisosteric Design Identifies Inhibitors of DNA Gyrase ATPase Activity.

Mutations in DNA gyrase confer resistance to fluoroquinolones, second-line antibiotics for infections. Identification of new agents that inhibit DNA gyrase ATPase activity is one strategy to overcome this. Here, bioisosteric designs using known inhibitors as templates were employed to define novel inhibitors of DNA gyrase ATPase activity.