Laboratory of Nucleic Acids Derivatives Synthesis


Head:

Prof. Tomasz Ostrowski,

 

 


Staff:

Dr. Grzegorz Framski,

Dr. Maurycy Szlenkier

 

 


 

Rys.1

 


Rys.2


 

 

 

 

 

 

 

 

 

 

Keywords:

organic synthesis, nucleoside analogues, purine nucleosides, pyrimidine nucleosides, 1,2,3-triazole nucleosides, acyclic nucleosides, nucleotide analogues, pronucleotides, antiviral activity, anticancer activity, antibacterial activity, structure – activity relationship

 

Research offer:

Synthesis of heterocyclic compounds with particular emphasis on modified nucleobases, nucleosides and nucleotides.

 

Equipment:

Standard equipment of organic chemistry lab

 

Scientific profile:

Laboratory of Nucleic Acids Derivatives Synthesis was set up in September 2015 and brings together three people working previously in the Department of Nucleic Acids Chemistry, Institute of Bioorganic Chemistry, PAS, headed by Prof. Adam Kraszewski (in the Group of Nucleoside Chemistry or in the Group of Pronucleotides). Research in the Laboratory includes the synthesis of purine, pyrimidine and 1,2,3-triazole nucleosides, sugar-modified nucleosides, as well as nucleotide analogues, focused on compounds with required physicochemical properties and potential biological activities.

 

Current research activity:

  • synthesis of modified purine nucleosides for the purpose of examination of their activities and mechanisms of action in cancer cells
  • studies on reactivity of 9-substituted guanine system
  • synthesis of new pronucleotides with potential anticancer activities and investigation of their metabolic pathways

 

Most important research achievements of Laboratory members:

  • synthesis of the series of tricyclic guanine acyclonucleoside analogues exhibiting potent antiviral activities and cytostatic activities in the experiments of gene/chemotherapy of cancer
  • synthesis of 5-alkynyl-1H-[1,2,3]triazole-4-carboxamide ribofuranosides possessing interesting antiviral properties, potential precursors of inosine 5’-monophosphate dehydrogenase inhibitors
  • contribution to preparation of 2-aryl derivatives of 5’-O-[N-(salicyl)sulfamoyl]-8-aza-3-deazaadenosine shown to inhibit the mycobactin biosynthesis and to demonstrate antitubercular activities
  • contribution to the studies on the application of chemistry of nucleoside analogue phosphonates in the synthesis of potential biologically relevant antiviral pronucleotides; preparation of highly active and selective anti-HIV (N-aryl)phosphoramidates
  • synthesis of the series of 3’-O-acyl 5-fluoro-2’-deoxyuridine derivatives as potential anticancer prodrugs
  • elaboration of the synthetic method for nucleoside α-hydroxyphosphonate monoesters
  • synthesis of morpholine-based herbicidal ionic liquids for evaluation of their toxicity and biodegradability

 

Current research projects:

  • Kinetin riboside and its analogues – analysis of their apoptotic properties and mechanism of action in brain cancer cells (UMO-2014/13/B/NZ7/02291); head: Prof. Eliza Wyszko; execution within 2015-2018.

 

Selected publications of Laboratory members (2010-2016):

A.Szymańska-Michalak, J.Stawiński, A.Kraszewski
Studies on the decomposition pathways of diastereoisomeric mixtures of aryl nucleoside α-hydroxyphosphonates under hydrolytic conditions. Synthesis of α-hydroxyphosphonate monoesters.
New J. Chem. 34, 976-983 (2010)

T.Ostrowski, P.Januszczyk, M.Cieślak, J.Kaźmierczak-Barańska, B.Nawrot,E.Bartoszak-Adamska, J.Zeidler
5-Ethynyl-1-β-D-ribofuranosyl-1H-[1,2,3]triazole-4-carboxylic acid amide (ETCAR) and its analogues: synthesis and cytotoxic properties.
Bioorg. Med. Chem. 19, 4386-4398 (2011)

J.Romanowska, M.Sobkowski, A.Szymańska-Michalak, K.Kołodziej, A.Dąbrowska, A.Lipniacki, A.Piasek, Z.M.Pietrusiewicz, M.Figlerowicz, A.Guranowski, J.Boryski, J.Stawiński, A.Kraszewski
Aryl H-phosphonates 17: (N-aryl)phosphoramidates of pyrimidine nucleoside analogues and their synthesis, selected properties, and anti-HIV activity.
J. Med. Chem. 54, 6482-6491 (2011)

A.Krajczyk, K.Kulińska, T.Kuliński, B.L.Hurst, C.W.Day, D.F.Smee, T.Ostrowski,P.Januszczyk, J.Zeidler
Antivirally active ribavirin analogues – 4,5-disubstituted 1,2,3-triazole nucleosides: biological evaluation against certain respiratory viruses and computational modeling.
Antivir. Chem. Chemother. 23, 161-171 (2014)

M.A.Leśniewska, T.Ostrowski, J.Zeidler, I.Muszalska
Ester groups as carriers of antivirally active tricyclic analogue of acyclovir in prodrugs designing: synthesis, lipophilicity ­comparative statistical study of the chromatographic and theoretical methods, validation of the HPLC method.
Comb.Chem. High Throughput Screen. 17, 639-650 (2014)

J.Zeidler, D.Baraniak, T.Ostrowski
Bioactive nucleoside analogues possessing selected five-membered azaheterocyclic bases.
Eur. J. Med. Chem. 97, 409-418 (2015)

Ł.Ławniczak, K.Materna, G.Framski, A.Szulc, A.Syguda
Comparative study on the biodegradability of morpholinium herbicidal ionic liquids.
Biodegradation 26, 327-340 (2015)

A.Krajczyk, J.Zeidler, P.Januszczyk, S.Dawadi, H.I.Boshoff, C.E.Barry III, T.Ostrowski, C.C.Aldrich
2-Aryl-8-aza-3-deazaadenosine analogues of 5’-O-[N-(salicyl)sulfamoyl]adenosine: nucleoside antibiotics that block siderophore biosynthesis in Mycobacterium tuberculosis.
Bioorg. Med. Chem. 24, 3133-3143 (2016)

A.Szymańska-Michalak, D.Wawrzyniak, G.Framski, M.Kujda, P.Zgoła, J.Stawiński, J.Barciszewski, J.Boryski, A.Kraszewski
New 3’-O-aromatic acyl-5-fluoro-2’-deoxyuridine derivatives as potential anticancer agents.
Eur. J. Med. Chem. 115, 41-52 (2016)

 

Patents:

A.Kraszewski, J.Romanowska, M.Sobkowski, A.Szymańska-Michalak, J.Stawiński, J.Boryski, A.Lipniacki, A.Piasek

Nucleotide analogue, method of synthesis of nucleotide analogue, use of nucleotide analogue, antiviral pro-nucleotide, pharmaceutical composition.

European Patent No. EP 2630152 (2014)

United States Patent No. US 9,206,209 B2 (2015)