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Department of Organic Chemistry

Faculty of Science
Palacký University
Olomouc

Laboratory of Experimental Medicine

Departments of Pediatrics and Oncology
Faculty of Medicine
Palacký University and Faculty Hospital in Olomouc

Institutt for Farmasi

Universitetet i Tromsoe
Tromsoe
Norway
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The sub-project has been supported from the EEA/Norway Grants and the Czech Republic state budget by means of the Research Support Fund.


Published results

Minireviews in Medicinal Chemistry 2009, 9, 696-702.
2-Phenyl-3-hydroxy-4(1H)-quinolinones can be considered as aza-analogues of flavones, compounds which are known for the wide-range of their biological activity. These quinolinones were studied as inhibitors of topoisomerase, gyrase and IMPDH. They were tested for anticancer activity in-vitro and were also shown to possess immunosuppressive properties. This review is the first summarizing the synthesis and activity of the mentioned quinolinones.

European Journal of Organic Chemistry 2009, 3867–3870.
The preparation of novel organic disulfides containing the 2-(substituted phenyl)quinolin-4(1H)-one ring is described. The synthesis starts from thioanthranilic acid esterified with various bromoacetophenones. Cyclization of the resulting phenacyl thioanthranilates in trifluoroacetic acid afforded a mixture of 2-(substituted phenyl)-3-sulfanylquinolin-4(1H)- ones and 3,3_-disulfanediylbis[2-(substituted phenyl)quinolin-4(1H)-ones]. Heating of the mixture in o-xylene gave 3,3_- disulfanediylbis[2-(substituted phenyl)quinolin-4(1H)-ones] of high purity. The disulfides exhibited a significant in vitro cytotoxicity against various cancer cell lines including polyresistant subclones. The data obtained are reported and discussed.

Journal of Combinatorial Chemistry 2009, 11, 951-955.
The efficient solid-phase synthesis of 3-hydroxy-2,7-disubstituted-6-nitroquinolin-4(1H)-ones using Rink amide resin is described. Synthesis starts from immobilized 4-chloro-5-nitroanthranilic acid which, after the nucleophilic replacement of the chlorine atom with various amines and subsequent esterification with bromoacetophenones, afforded substituted phenacylanthranilates. Their cyclization by heating in sulfuric acid gave corresponding hydroxyquinolinones of excellent purity.

Monatshefte für Chemie / Chemical Monthly 2010, 141, 233-244.
New oleanane alcohols and their acetates were prepared using classical reductive reagents (LiAlH4, NaBH4, and B2H6-DMS). In this research, we also studied the influence of these reagents on the stereoselectivity of reduction. All compounds prepared were fully characterized by 1H and 13C NMR spectra, IR spectra, MS, and elemental analysis. These products were tested for cytotoxin activity against T-lymphoblastic leukemia (CEM), human erythromyeloblastoid leukemia (K562), and human melanoma (SK-MEL1) cell lines. One of the compounds prepared exhibits significant cytotoxic activity against the mesenchymal type of cancer cell lines.

Patent CZ 301318 (Univerzity of Palacky) 2009
The patent describes use of 2-deoxyglycosides derived from triterpenoides for treatment of cancer diseases and disorders caused by pathologic proliferation. The derivatives were found to be active against e.g. leukemia, lung cancer, colorectal carcinoma and glioblastoms. Newly these derivatives were found to be active against specific childhood tumors. The claims of this patent include preparation of these derivatives based on reaction of triterpenic hydroxyderivatives with acetylated glycals affording acetylated 2-deoxyglycoside triterpenoids, that can also be deacetylated.

Technologies transfered

  1. Effective mode of biotinylation of carboxylic compounds with use of solid phase synthesis for affinity chromatography purposes.
  2. Effective mode of biotinylation of amines with use of solid phase synthesis for affinity chromatography purposes.
These technologies are suitable for effective biotinylation of various derivatives bearing carboxylic or amino group in their structure. These biotinylated products can be used in affinity chromatography as a tool for molecular target identification. The technologies were licensed.
© Department of Organic Chemistry, Palacky University Olomouc, Czech Republic