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Plasticity of the Mycobacterium tuberculosis respiratory chain and its impact on tuberculosis drug development
It is demonstrated that an Mtb cytochrome bc1-aa3 oxidase deletion mutant is viable and only partially attenuated in mice, and the intrinsic plasticity of Mtb’s respiratory chain is demonstrated, highlighting the challenges associated with targeting the pathogen's respiratory enzymes for tuberculosis drug development. Expand
A remote-controlled adaptive medchem lab: an innovative approach to enable drug discovery in the 21st Century.
This article describes the experiences in creating a fully integrated, globally accessible, automated chemical synthesis laboratory that was initially focused on minimizing the burden of repetitive, routine, rules-based operations that characterize more established chemistry workflows. Expand
Prediction of Drug Penetration in Tuberculosis Lesions.
It is shown that binding to caseum inversely correlates with passive diffusion into the necrotic core of tuberculosis drugs, and a rule of thumb was derived whereby the sum of the hydrophobicity (clogP) and aromatic ring count is proportional to caseu binding. Expand
Identification of Morpholino Thiophenes as Novel Mycobacterium tuberculosis Inhibitors, Targeting QcrB
With the emergence of multidrug-resistant strains of Mycobacterium tuberculosis there is a pressing need for new oral drugs with novel mechanisms of action. Herein, we describe the identification ofExpand
Synthesis and Evaluation of the 2-Aminothiazoles as Anti-Tubercular Agents
The 2-aminothiazole series has anti-bacterial activity against the important global pathogen Mycobacterium tuberculosis and has potential for further development as novel anti-tubercular agents. Expand
Improved Phenoxyalkylbenzimidazoles with Activity against Mycobacterium tuberculosis Appear to Target QcrB
The most potent compounds had minimum inhibitory concentrations against Mycobacterium tuberculosis in the low nanomolar range with very little cytotoxicity against eukaryotic cells as well as activity against intracellular bacteria. Expand
A Novel Approach towards 2,3,5‐Trisubstituted Thiophenes via tandem Michael addition/intramolecular Knoevenagel condensation
Starting from the easily available, highly functionalized acetylenic ketories 4a–i (Scheme 1), novel 2,3,5-trisubstituted thiophenes 1a–i (Scheme 2) were synthesized in good yields using a tandemExpand
Identification of Compounds with pH-Dependent Bactericidal Activity against Mycobacterium tuberculosis
Five compounds that disrupt intrabacterial pH homeostasis are selected and demonstrated bactericidal activity against nonreplicating bacteria in buffer and are useful starting points for work to elucidate their mechanism of action and their utility for drug discovery. Expand
Investigation of retention behavior of drug molecules in supercritical fluid chromatography using linear solvation energy relationships.
The LSER results showed that the SFC retention behavior of compounds using carbon dioxide-methanol with polar stationary phases was close to that reported for normal phase LC using hexane- methanol. Expand
Identification of Phenoxyalkylbenzimidazoles with Antitubercular Activity.
The results indicate that the readily synthesized phenoxyalkylbenzimidazoles are a promising class of potent and selective antitubercular agents, if the metabolic liability can be solved. Expand