Design and development of novel therapeutics for brucellosis treatment based on carbonic anhydrase inhibition.

Carbonic anhydrase is a metalloprotein, an enzyme with strong inhibition in antibacterial treatment. This study presents QSAR modeling for a series of 41 chemical compounds, 40 sulfonamides and one sulfamate, including 13 clinically tested drugs as carbonic anhydrase inhibitors based on the Monte Carlo optimization with molecular descriptors based on the SMILES notation and local invariants of the molecular graph, and field 3D based methods. Conformation independent QSAR models were developed for three random splits and a 3D QSAR model for one random split into the training and test sets. The statistical quality of the developed models, including robustness and predictability, was tested using various statistical approaches and the results that were obtained were very good. An excellent correlation between the results from the conformation independent and the 3D QSAR model was obtained. A novel statistical metric known as the index of ideality of correlation was used for the final assessment of the model, and the obtained results were good. Molecular fragments responsible for the increases and decreases of a studied activity were defined and further used for the computer-aided design of new compounds as potential carbonic anhydrase inhibitors. Molecular docking was applied for the final assessment of the developed QSAR model and designed inhibitors, and an excellent correlation between the results from QSAR modeling and molecular docking studies was obtained.Communicated by Ramaswamy H. Sarma.

Correlation between nonalcoholic fatty liver and cardiovascular disease in elderly hemodialysis patients.

PURPOSE: The number of elderly patients with end-stage kidney disease is on the rise. Nonalcoholic fatty liver disease (NAFLD) is characterized by parenchymal fat accumulation in patients without information about alcohol abuse. The aim of our study was to determine correlation between NAFLD and cardiovascular diseases in elderly hemodialysis patients. METHODS: The examination was organized as observational and cross-sectional study in elderly patients on hemodialysis. An abdominal ultrasound examination was made in order to define NAFLD. Intima-media thickness of the carotid arteries was quantified by Doppler ultrasound. Biochemical parameters, gender, anthropometric characteristics, duration, adequacy of hemodialysis, blood pressure, smoking and cardiovascular disease were determined. Respondents were divided into a group with NAFLD (37/72 patients, 51 %) and group without NAFLD (35/72 patients, 49 %). RESULTS: Patients with NAFLD have significantly more cardiovascular disease (p = 0.017) as well as significantly higher values of intima-media thickness of the carotid arteries (p = 0.03) in correlation with patients without NAFLD. Patients without NAFLD have a statistically lower triglyceride (p = 0.04), aspartate aminotransferase (p = 0.006), alanine aminotransferase (p = 0.013) and gamma-glutamyl transpeptidase (p = 0.029) compared to patients with NAFLD. Patients with cardiovascular disease have a higher risk of NAFLD; likewise, patients with NAFLD have a three times higher chance for developing cardiovascular diseases (OR 3.01). CONCLUSION: Elderly patients on hemodialysis with cardiovascular disease have a higher risk of NAFLD; likewise, patients with NAFLD have a three times higher chance for developing cardiovascular diseases.