X-ray structural analysis and antitumor activity of new salicylic acid derivatives

This Thesis project is going to be situated in my home town Östersund, 600 kilometers north from Stockholm.It´s a small town with 60 000 people and it is the only city of the region Jämtland in Norrland, Sweden.In the city centre of Östersund there is one existing bus terminal station where the buses arrive with people from the entire region.The task for this Thesis project is to rebuild the existing bus station in Östersund where the actual terminal building is going to be completely demolished and the entire block within the current bus stops is going to be rearranged.The topography of the terminal area is now dividing the regional buses that arrives on the upper level from the city buses that stops at the lower level. Therefore the main challenge of the new proposal is how one would strengthen the junction between these two flows of people and how a new architecture could enable the encounter between the countryside and the urban city.Detta examensprojekt kommer att vara belägen i min hemstad Östersund, 600 kilometer norr om Stockholm. Det är en liten stad med 60 000 personer och det är den enda staden i regionen Jämtland, Norrland. I centrum av Östersund finns en befintlig bussterminalen där bussarna anländer med folk från hela regionen. Uppgiften för detta projekt är att bygga om den befintliga busstationen i Östersund topografin på terminalområdet i dagsläget separerar de regionala bussarna som anländer på den övre nivån från stadsbussarna som stannar på en lägre nivå. Den största utmaningen i det nya förslaget är hur man istället skulle kunna stärka förbindelsen mellan dessa två flöden av människor och hur en ny arkitektur kan möjliggöra mötet mellan glesbyggd och den urbana staden

Further in vitro evaluation of cytotoxicity of the marine natural product derivative 4 '-leucine-avarone

The cytotoxicity of 4-leucine-avarone, amino derivative of the sponge Dysidea avara secondary metabolite avarone, was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay in vitro against seven human solid tumours for the first time. The compound tested induced dose-dependent cytotoxic response in all cancer cells showing better activity towards the lung A-549 and colon HT-29 cell lines (IC50 7.40M and 9.62M, respectively) than towards the breast adenocarcinoma ER positive MCF-7 and ER negative MDA-MB-231 cells (IC50 11.64M and 17.31M, respectively), the prostate adenocarcinoma PC-3 and epiteloid cervix carcinoma HeLa cells (IC50 14.24M and 15.54M, respectively). No toxicity was found towards the foetal lung fibroblast MRC-5 cell line at the concentrations used. According to experimental data obtained, the sesquiterpenoid quinone structure of avarone may inspire development of new drug-like substances with improved cytotoxicity on lung cancer in humans

Time-dependent inhibition of Na+/K+-ATPase induced by single and simultaneous exposure to lead and cadmium

Time-dependent interactions of Na+/K+-ATPase, isolated from rat brain synaptic plasma membranes (SPMs), with Cd2+ and Pb2+ ions in a single exposure and in a mixture were investigated in vitro. The interference of the enzyme with these metal ions was studied as a function of different protein concentrations and exposure time. The aim of the work was to investigate the possibility of selective recognition of Cd2+ and Pb2+ ions in a mixture, on the basis of the different rates of their protein-ligand interactions. Decreasing protein concentration increased the sensitivity of Na+/K+-ATPase toward both metals. The selectivity in protein-ligand interactions was obtained by variation of preincubation time (incubation before starting the enzymatic reaction).8th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Sep 26-29, 2006, Belgrade, Serbi

Rhodium(III) in a cage of the 1,3-propanediamine-N,N,N′-triacetate chelate: X-ray structure, solution equilibria, computational study and biological behavior

Two new octahedral Rh(III) complexes that are potential chemotherapeutic agents have been synthesized from the 1,3-propanediamine-N,N,N’-triacetate ligand (1,3-pd3a): [Rh(1,3-pd3a)(H2O)]·2H2O (1) and Na[Rh(1,3-pd3a)Cl]·2H2O (2). Both complexes were characterized by IR, UV–Vis and NMR spectroscopy, as well as elemental analysis. Only the structure of 2 was determined by a single crystal X-ray diffraction study. The asymmetric unit contains the negatively charged rhodium complex, a sodium ion and two water molecules. The positions of the carboxylate groups define the cis-polar geometry. DFT calculations on 1 and 2 have also been done to confirm experimental results. In order to determine the protonation constants of 1,3-H3pd3a, stability constants and the stoichiometry of the complexes in aqueous solution, pH-potentiometry and UV–Vis spectrophotometry were used. Docking of 1 to human serum albumin (HSA) gives the reasonable assumption that this complex can be easily transported to the target cells. The complexes, as well as the 1,3-pd3a and ed3a ligands, were tested against various cancer and one normal human cell lines. Complex 2 and both ligands display significant cytotoxicity against the HeLa cancer cell line, while 1 shows good antitumor activity against MCF-7. Flow cytometry analysis showed the apoptotic death of the cells with cell cycle arrest in the G2/M phase (Na[Rh(1,3-pd3a)Cl]·2H2O) and G0/G1 phase (1,3-pd3a)

Antioxidant and cytotoxic activity of mono- And bissalicylic acid derivatives

A simple synthesis of mono- and bis-salicylic acid derivatives 1-10 by the transesterification of methyl salicylate (methyl 2-hydroxybenzoate) with 3-oxapentane-1,5-diol, 3,6- dioxaoctane-1,8-diol, 3,6,9-trioxaundecane-1,11-diol, propane-1,2-diol or 1-aminopropan- 2-ol in alkaline conditions is reported. All compounds were tested in vitro on three malignant cell lines (MCF-7, MDA-MB-231, PC-3) and one non-tumor cell line (MRC- 5). Strong cytotoxicity against prostate PC-3 cancer cells expressed compounds 3, 4, 6, 9 and 10, all with the IC50 less than 10 μmol/L, which were 11-27 times higher than the cytotoxicity of antitumor drug doxorubicin. All tested compounds were not toxic against the non-tumor MRC-5 cell line. Antioxidant activity of the synthesized derivatives was also evaluated. Compounds 2, 5 and 8 were better OH radical scavengers than commercial antioxidants BHT and BHA. The synthesized compounds showed satisfactory scavenger activity, which was studied by QSAR modeling. A good correlation between the experimental variables IC50 DPPH and IC50 OH and MTI (molecular topological indices) molecular descriptors and CAA (accessible Connolly solvent surface area) for the new compounds 1, 3, and 5 was observed