Iron chelating, antioxidant, and anti-inflammatory properties of brazilin from Linn.

Background: Iron overload and inflammation are severe conditions that can lead to various chronic diseases. However, the current iron chelator drugs have their limitations. The phytochemical compounds from herbals, such as brazilin, the major active compound in Linn.

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.

Elucidating specific interactions for designing novel pyrrolamide derivatives as potential GyrB inhibitors based on fragment molecular orbital calculations.

Tuberculosis (TB), the second leading infectious killer, causes serious public health problems worldwide. To develop novel anti-TB agents, many biochemical studies have targeted the subunit B of DNA gyrase (GyrB), which captures a second DNA segment and responses for ATP hydrolysis. Here, we investigated specific interactions between GyrB residues and existing pyrrolamide derivatives at an electronic level using fragment molecular orbital (FMO) calculations and designed potent inhibitors against GyrB.

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.

Structure-based drug design of novel M. tuberculosis InhA inhibitors based on fragment molecular orbital calculations.

2-trans enoyl-acyl carrier protein reductase (InhA) is a promising target for developing novel chemotherapy agents for tuberculosis, and their inhibitory effects on InhA activity were widely investigated by the physicochemical experiments. However, the reason for the wide range of their inhibitory effects induced by similar agents was not explained by only the difference in their chemical structures. In our previous molecular simulations, a series of heteroaryl benzamide derivatives were selected as candidate inhibitors against InhA, and their binding properties with InhA were investigated to propose novel derivatives with higher binding affinity to InhA.

Virtual Screening Identifies Novel and Potent Inhibitors of PknB with Antibacterial Activity.

protein kinase B (PknB) is essential to mycobacterial growth and has received considerable attention as an attractive target for novel anti-tuberculosis drug development. Here, virtual screening, validated by biological assays, was applied to select candidate inhibitors of PknB from the Specs compound library (www.specs.

In silico design of novel quinazoline-based compounds as potential Mycobacterium tuberculosis PknB inhibitors through 2D and 3D-QSAR, molecular dynamics simulations combined with pharmacokinetic predictions.

Serine/threonine protein kinase B (PknB) is essential to Mycobacterium tuberculosis (M. tuberculosis) cell division and metabolism and a potential anti-tuberculosis drug target. Here we apply Hologram Quantitative Structure Activity Relationship (HQSAR) and three-dimensional QSAR (Comparative Molecular Similarity Indices Analysis (CoMSIA)) methods to investigate structural requirements for PknB inhibition by a series of previously described quinazoline derivatives.

Identification of Potent DNA Gyrase Inhibitors Active against .

DNA gyrase manipulates the DNA topology using controlled breakage and religation of DNA driven by ATP hydrolysis. DNA gyrase has been validated as the enzyme target of fluoroquinolones (FQs), second-line antibiotics used for the treatment of multidrug-resistant tuberculosis. Mutations around the DNA gyrase DNA-binding site result in the emergence of FQ resistance in ; inhibition of DNA gyrase ATPase activity is one strategy to overcome this.