Aminobenzimidazole inhibitors of GyrB exhibit many of the characteristics required for their consideration as a potential front-line antimycobacterial therapeutic.

Synthetic derivatives of the natural product antibiotic novobiocin were synthesized in order to improve their physiochemical properties. A Mannich reaction was used to introduce new side chains at a solvent-exposed position of the molecule, and a diverse panel of functional groups was evaluated at this position. Novobiocin and the new derivatives were tested for their binding to gyrase B and their antibacterial activities against S. aureus, M. tuberculosis, F. tularensis and E. coli. While the new derivatives still bound the gyrase B protein potently (0.07 – 1.8 μM IC50), they had significantly less antibacterial activity. Two compounds were identified with increased antibacterial activity against M. tuberculosis, with a minimum inhibitory concentration of 2.5 μg/ml.

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The prevalence of kidney disease is high. Most drugs are excreted by the kidneys and drug dosage adjustments are likely required in renal impairment to avoid accumulation and exposure-related toxicity. Kidney disease affects physiological changes and alterations in the pharmacokinetics and the pharmacodynamics of many drugs. Glomerular filtration rate is considered the best overall index of kidney function. Kidney function can be assessed by using endogenous and exogenous markers such as serum creatinine, inulin, cystatin C, radionuclide-labeled, estimated equations for creatinine clearance such as Cockcroft-Gault, and estimated equations for GFR such as the Modification of Diet in Renal Disease study equation, and the Chronic Kidney Disease Epidemiology Collaboration Epidemiology study equation. Applying good prescribing practice is important for limiting drug toxicities and improving patient care.