The aim of the study is to evaluate the influence of angiotensin converting enzyme (ACE) inhibitors of quinapril on the condition of renal hemodynamics, changes of profibrotic cytokines level and transforming growth factor at patients with nephrolithiasis undergone various kinds of surgery. Patients were divided into 2 groups initially and in 1 month after surgery. Concentrations of IL-6, TGFp and МСР-1 were determined in blood serum. Assessment of renal blood flow state by Doppler ultrasonography was performed in the same terms. As a result of quinapril treatment the decrease of МСР-1, TGFp and IL-6 was marked in comparison with the group which did not receive nephroprotective therapy. The analysis of Doppler ultrasonography data showed authentic improvement of renal blood flow in 1 month after surgery. The most informative parameter proved to be the resistance index that indicated the decrease of vascular resistance after surgical treatment in condition of quinapril therapy
P.V. Glybochko, A.A. Svistunov, A.N. Rossolovsky, O.L. Berezinetz, N.B. Zakharova, A.P. Abramova State of renal hemodynamics and nephrofibrosis parameters in patients with nephrolithiasis applying angiotensin converting enzyme inhibitors // Saratov Journal of Medical Scientific Research, Vol. 6, Issue 1, 2010, pp. 170-173

The prediction of biological activity spectra for substances as an approach for searching compounds with complex mechanisms of action was studied. New compounds with dual mechanisms of antihypertensive action were found by this approach. Biological activity spectra for substances were predicted on the basis of their structural formulas by the computer program PASS. Thirty molecular mechanisms of action of compounds from the MDDR 99.2 database, which cause the antihypertensive effect and can be predicted by PASS, have been identified. The analysis of predictions for compounds with 15 dual antihypertensive mechanisms of action from the MDDR 99.2 database has confirmed high accuracy of prediction. This approach was applied to databases of commercially available compounds (AsInEx and ChemBridge) and allowed us to select four substances that are potential inhibitors of angiotensin converting enzyme (ACE) and of neutral endopeptidase (NEP). At a later time, all these compounds were found to be the inhibitors of both ACE and NEP. The most potent compounds had IC50 of 10-7 - 10-9 M for ACE and 10-5 M for NEP. New combinations of dual mechanisms of action never before found for antihypertensive compounds were predicted.
Journal of Medicinal Chemistry, 2003, 46 (15), 3326-3332.