ABSTRACT
Herein, a robust docking protocol was developed by using a low-cost workflow to highlight the modulation at ATPase domain from Human Topoisomerase-IIα (TOP2A) towards four novel Pd(II)-complexes bearing N,S-donor ligands. In vitro TOP2A inhibition assay confirmed the ability of them to prevent the enzyme functions into concentration ranging at 6.25-25µM. These results exhibited more effectivity than anticancer agent etoposide (35µM) and merbarone (40-50µM). The compounds were screened via Resazurin assay against MCF-7, MDA-MB-231 (Human breast), DU-145 (Human prostate), A549 (Human lung) and Cal27 (Human tongue) tumor cell lines revealing great cytotoxic effects, primarily to MCF-7 (IC50=1.81-4.46µM). As well, 1-4 exhibited their selectivity index (SI) higher than cisplatin against HEK-293 (human kidney) normal cells, at least 11.6-fold (SI1-4=1.4-5.0; SIcis=0.12). Further, Red Blood Cell hemolytic test suggested in vitro non-toxic character for compound 4, previously evaluated as the most effective TOP2A inhibitor.
Subject(s)
DNA Topoisomerases, Type II/metabolism , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Palladium/chemistry , A549 Cells , Allosteric Regulation , Antineoplastic Agents/adverse effects , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Enzyme Inhibitors/adverse effects , Enzyme Inhibitors/chemical synthesis , Hemolysis/drug effects , Humans , MCF-7 Cells , Molecular Docking Simulation , Molecular Structure , Structure-Activity Relationship , Topoisomerase II Inhibitors/adverse effects , Topoisomerase II Inhibitors/chemical synthesis , Topoisomerase II Inhibitors/chemistry , Topoisomerase II Inhibitors/pharmacologyABSTRACT
The title mol-ecule, C9H7BrN4OS, is essentially planar [r.m.s. deviation = 0.066â (2)â Å], the maximum deviation from the mean plane through the non-H atoms being 0.190â (3)â Å for the terminal amine N atom. In the crystal, mol-ecules are linked through N-Hâ¯O and N-Hâ¯S inter-actions, generating infinite chains along the b-axis direction. In turn, the chains are stacked along the a axis via π-π inter-actions [centroid-centroid distance = 3.470â (2)â Å] and further connected by N-Hâ¯Br inter-actions into a three-dimensional network. An intra-molecular N-Hâ¯O hydrogen bond is also observed.
ABSTRACT
The present work describes the substantial electrocatalytic activity of (NC)2C6H3-NHOH/(NC)2C6H3-NO redox couple-modified electrode toward the low voltage detection of l-glutathione (GSH), in neutral medium, at an applied potential of 0.4V versus Ag/AgCl. After optimizing the operational conditions, the sensor provided a linear response range for GSH from 8.0 up to 83.0 micromol L(-1) with sensitivity, detection and quantification limits of 54nA L micromol(-1), 2.7 micromol L(-1) and 8.0 micromol L(-1), respectively. The proposed sensor presented higher sensitivity when compared to other modified electrodes described in the literature and showed a stable response for at least 100 successive determinations. The repeatability of the measurements with the same sensor and different sensors, evaluated in terms of relative standard deviation, were 4.1 and 5.0%, respectively, for n=10. The developed sensor was applied for GSH determination in yeast extract and the results were statistically the same with those obtained by the comparative method described in the literature at a confidence level of 95%.
Subject(s)
Biosensing Techniques/methods , Electrochemistry/methods , Glutathione/analysis , Nitriles/chemistry , Biosensing Techniques/instrumentation , Buffers , Catalysis , Electrochemistry/instrumentation , Electrodes , Feasibility Studies , Hydrogen-Ion Concentration , Oxidation-Reduction , Reproducibility of Results , Saccharomyces cerevisiae/chemistry , Sensitivity and SpecificityABSTRACT
The effectiveness of an aqueous extract of Caryocar brasiliense (Caryocaraceae) Camb pulp, popularly known in Brazil as pequi, against clastogenicity induced by cyclophosphamide and bleomycin was evaluated using an in vivo mouse bone marrow cell micronuclei test, an in vitro Chinese hamster ovary cell (CHO-K1) chromosome aberration test and an in vitro antioxidant assay based on the oxidative damage to 2-deoxy-D-ribose (2-DR) induced by hydroxyl radicals (OH) generated by the reaction between ascorbic acid and (Fe III)-EDTA. In mouse bone marrow cells the extract showed a protective effect against micronuclei induced by cyclophosphamide and bleomycin but did not interfere with polychromatic bone marrow erythrocyte proliferation, except when the mice had been treated with the highest dose of cyclophosphamide. When CHO-K1 cells were pretreated by adding 0.01, 0.05 or 0.1 mL of extract per mL of cell culture medium 24 or 48 h before bleomycin or cyclophosphamide there was a protective effect against chromosome breaks and a significant decrease in the mitotic index (a measure of cytotoxicity) of the CHO-K1 cells. The extract also had a protective effect against oxidative hydroxyl radical damage to 2-DR. This study suggests that C. brasiliense pulp aqueous extract has anticlastogenic potential, possibly due to its antioxidative properties.
