Estimating Unbound Drug Concentrations in Simulated Human Lung Fluid: Relevance to Lung Antibiotic PKPD.

The use of unbound drug concentrations is crucial for the prediction of efficacious doses. Hence, dose predictions for antibiotics targeting respiratory pathogens should be based on free, rather than the currently used, total drug concentrations in epithelial lining fluid (ELF). In this work, we describe an assay to estimate the percent unbound of drugs in ELF using simulated epithelial lining fluid (sELF) containing the most abundant components of ELF in healthy humans.

Synthesis, cytostatic activity and ADME properties of C-5 substituted and N-acyclic pyrimidine derivatives.

The synthesis of the novel 5-alkyl pyrimidine derivatives, 5,6-dihydrofuro[2,3-d]pyrimidines and 5-alkyl N-methoxymethyl pyrimidine derivatives and evaluation of their cytostatic activities are described. The mechanism of antiproliferative effect of 5-(2-chloroethyl)-substituted pyrimidine 3 that exerted the pronounced cytostatic activity was studied in further details on colon carcinoma (HCT116) cells. The cell cycle perturbation analysis demonstrated severe DNA damage (G2/M arrest) pointing to a potential DNA alkylating ability of 3.

Crystal structure and physicochemical properties of crystalline form of 2'-O-{3-[(7-chloro-4-quinolinyl)amino]propyl}-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A.

The intent of the study was to prepare and characterize crystalline form of 2'-O-{3-[(7-chloro-4-quinolinyl)amino]propyl}-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A (1), a novel 15-membered azalide derivative with antimalarial activity. The crystalline material was prepared by crystallization from acetonitrile reproducible in high yield and purity. Single crystal X-ray studies, X-ray powder diffractometry, differential scanning calorimetry, thermogravimetric analysis, moisture adsorption, Karl Fischer titration, gas chromatography, scanning electron microscopy, optical microscopy, solubility, and solid-state and solution stability were conducted to investigate physicochemical properties of the existing crystalline form.