The role of modern genetic in prevention and diagnosis of rare diseases

In this paper, we deal with the problems encountered by those suffering from rare diseases and their families as well as the recommendations of the Council of Europe related to the activities in this field. It gives an estimate of the current situation in our country and emphasizes the need for adoption and implementation of National Plan/Strategy for rare diseases. Given the frequent dependence existing between these diseases and genetic changes, preventive and diagnostic measures have to be based on the application of modern genetics along with upholding ethical principles

Synthesis, structural properties and DNA protective activity of ferrocenyl N-acyl pyrazolines

Two series of new ferrocenyl pyrazolines have been synthesized by the reac-tion of ferrocenyl chalcones and their analogues with hydrazine hydrate in thepresence of corresponding carboxylic acid. Single-crystal X-ray crystallographicdata were used for detailed analysis of the interesting versatility of four com-pounds in the formation of intermolecular interactions. The analysis revealedan excellent structural flexibility of the present ferrocenyl pyrazoline moleculesfor the non-covalent interactions, with a particular contribution of the ferro-cene units. In addition, for comparison with crystallographic findings, weinvestigated the protective effect of all compounds on DNA against hydroxyland peroxyl radicals induced by Fe2+,H2O2, and 2,20-azobis(2-amidinopro-pane) dihydrochloride (AAPH). The results indicated that all compoundsshowed rather similar DNA protective activity, which was comparable withquercetin as a well-known protective compound. This similarity in antigeno-toxic action could be explained by the established excellent structural flexibil-ity of ferrocenyl pyrazolines for the formation of different intermolecularinteractions as important structural property for molecular recognition

Synthesis, characterization, anticancer evaluation and mechanisms of cytotoxic activity of novel 3-hydroxy-3-pyrrolin-2-ones bearing thenoyl fragment: DNA, BSA interactions and molecular docking study

In order to make a progress in discovering a new agents for chemotherapy with improved properties and bearing in mind the fact that substituted 3-hydroxy-3-pyrrolin-2-ones belong to a class of biologically active compounds, series of novel 1,5-diaryl-4-(2-thienylcarbonyl)-3-hydroxy-3-pyrrolin-2-ones were synthesized and characterized by spectral (UV–Vis, IR, NMR, ESI-MS), X-ray and elemental analysis. All compounds were examined for their cytotoxic effect on human cancer cell lines HeLa and MDA-MB 231 and normal fibroblasts (MRC-5). Four compounds, 3-hydroxy-1-(p-tolyl)-4-(2-thienylcarbonyl)-5-(4-chlorophenyl)-2,5-dihydro-1H-pyrrol-2-one (D10), 3-hydroxy-1-(3-nitrophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D13), 3-hydroxy-1-(4-nitrophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D14), and 3-hydroxy-1-(4-chlorophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D15), that showed the highest cytotoxicity against malignant cells and the best selectivity towards normal cells were selected for further experiments. Results obtained by investigating mechanisms of cytotoxic activity suggest that selected 3-hydroxy-3-pyrrolin-2-one derivatives in HeLa cells induce apoptosis that is associated with S phase arrest (D13, D15, and D10) or unrelated to cell cycle distribution (D14). Additionally, to better understand their suitability for potential use as anticancer medicaments we studied the interactions between biomacromolecules (DNA or BSA) and D13 and D15. The results indicated that D13 and D15 have great affinity to displace EB from the EB-DNA complex through intercalation [K sv = (3.7 ± 0.1) and (3.4 ± 0.1) × 10 3 M −1 , respectively], an intercalative mode also confirmed through viscosity measurements. K a values, obtained as result of fluorescence titration of BSA with D13 and D15 [K a = (4.2 ± 0.2) and (2.6 ± 0.2) × 10 5 M, respectively], support the fact that a significant amount of the tested compounds could be transported and distributed through the cells. In addition, by DNA and BSA molecular docking study for D13, D14 and D15 is determined and predicted the binding mode and the interaction region. © 2019 Elsevier Inc.Peer-reviewed version of the article (Accepted Manuscript or postprint) available at: [https://vinar.vin.bg.ac.rs/handle/123456789/8186