Development of non-peptide ACE inhibitors as novel and potent cardiovascular therapeutics: An in silico modelling approach.

Angiotensin-converting enzyme (ACE) inhibitors have been acknowledged as first-line agents for the treatment of hypertension and a variety of cardiovascular disorders. In this context, quantitative structure-activity relationship (QSAR) models for a series of non-peptide compounds as ACE inhibitors are developed based on Simplified Molecular Input-Line Entry System (SMILES) notation and local graph invariants. Three random splits into the training and test sets are used. The Monte Carlo method is applied for model development. Molecular docking studies are used for the final assessment of the developed QSAR model and the design of novel inhibitors. The statistical quality of the developed model is good. Molecular fragments responsible for the increase/decrease of the studied activity are calculated. The computer-aided design of new compounds, as potential ACE inhibitors, is presented. The predictive potential of the applied approach is tested, and the robustness of the model is proven using different methods. The results obtained from molecular docking studies are in excellent correlation with the results from QSAR studies. The presented study may be useful in the search for novel cardiovascular therapeutics based on ACE inhibition.

Correlation of thermal deficit with clinical parameters and functional status in patients with unilateral lumbosacral radiculopathy.

INTRODUCTION: Lumbosacral radiculopathy is a pathological process that refers to the dysfunction of one or more spinal nerve roots in the lumbosacral region of the spine. Some studies have shown that infrared thermography can estimate the severity of the clinical manifestation of unilateral lumbosacral radiculopathy. This study aimed to examine the correlation of the regional thermal deficit of the affected lower extremity with pain intensity, mobility of the lumbar spine, and functional status in patients with unilateral lumbosacral radiculopathy. METHODS: This cross-sectional study was conducted at the Clinic for Physical Medicine and Rehabilitation of the Clinical Center Nis, Serbia. A total of 69 patients with unilateral lumbosacral radiculopathy of discogenic origin were recruited, with the following clinical parameters evaluated: (1) pain intensity by using a visual analogue scale, separately at rest and during active movement; (2) mobility of the lumbar spine by Schober test and the fingertip-to-floor test; and (3) functional status by the Oswestry Disability Index. Temperature differences between the symmetrical regions of the lower extremities were detected by infrared thermography. A quantitative analysis of thermograms determined the regions of interest with maximum thermal deficit. Correlation of maximum thermal deficit with each tested parameter was then determined. RESULTS: A significant and strong positive correlation was found between the regional thermal deficit and pain intensity at rest, as well as pain during active movements (rVAS - rest=0.887, rVAS - activity=0.890; P<0.001). The regional thermal deficit significantly and strongly correlated with the Oswestry Disability Index score and limited mobility of the lumbar spine (P<0.001). CONCLUSIONS: In patients with unilateral lumbosacral radiculopathy, the values of regional thermal deficit of the affected lower extremity are correlated with pain intensity, mobility of the lumbar spine, and functional status of the patient.