Screening laboratory

LP

Our main goal is to evaluate anti-cancer activity of low molecular compounds (natural or synthetic). To date more than 1000 organic compounds were characterized in terms of their cytotoxicity, but also as immunomodulators, nucleic acids carriers, DNA intercalators, alkylating agents, proapoptotic factors, and proteasome inhibitors. We also investigated mechanisms of their action and identified cellular protein targets. The obtained results were published in 27  papers and the intellectual property became covered by 6 patents.

 

In our Laboratory we have 15 cancer cell lines and several non-cancerous cell lines. We have instrumental and environmental facility appropriate for cells cultivation and quantification, as well as for analysis of the cellular uptake and intracellular distribution of investigated compounds and their metabolites in cells organelles.

Typically used analytical techniques include:

Determination of cytotoxicity (MTT test, ATP level)
Interactions with DNA

– ORD/CD, MALDI-TOF MS

– enzymatic assays

Detection of apoptosis (activity of caspases3/7/8/9, staining with annexin V/IP)
Gene expression analysis (real-time RT-PCR )
Analysis of cell cycle (flow cytometry)
Activity of proteasome
Signalling paths of MAPK kinases (Western blotting)
Analysis of immunomodulation activity (RT-PCR of mRNA of cytokines important for the immune system)
anti-oxidative activity and ROS level determination
identification of cellular protein targets using a pull-down method (with biotinylated probes) and mass spectrometry analysis
validation of the cellular protein targets (Western blotting, RNAi, microscale thermophoresis  – MST).

Our research:

  • is supported by governmental agencies and biotechnological companies
  • is based on collaboration with Research Institutes in Poland and abroad (presently with Warsaw Medical University, M. Nencki Institute of Experimental Biology PAS, Lodz Medical University, Maria Curie-Sklodowska University in Lublin, Ludwig Maximilian University Munchen, Institute of Bioorganic Chemistry in Poznan, Pharmaceutical Institute in Warsaw)
  • can be performed on a commercial basis – for more information (terms of scientific cooperation, the cost of tests) – please contact Prof. Barbara Nawrot (bnawrot@cbmm.lodz.pl) or Dr. Marcin Cieslak (marcin@cbmm.lodz.pl).

 

Achievements: 27 scientific publications and 10 patents (6 PL and 4 EPO patents).

  1. Cieślak MJ., Kaźmierczak-Barańska J., Królewska-Golińska K.,  Napiórkowska M.,  Stukan I., U. Wojda.,  Nawrot B. New thalidomide – resembling dicarboximides target ABC50 protein and show antileukemic and immunomodulatory activities. Biomolecules 2019, doi: 10.3390/biom9090446
  2. Kaleta B, Górski A, Zagożdżon R, Cieślak M, Kaźmierczak-Barańska J, Nawrot B, Klimaszewska M, Malinowska E, Górska S, Turło J. Selenium-containing polysaccharides from Lentinula edodes-Biological activity. Carbohydr Polym.2019, 1;223:115078
  3. Kost B, Brzeziński M, Cieślak M, Królewska-Golińska K, Makowski T, Socka M, Biela T. Stereocomplexed micelles based on polylactides with β-cyclodextrin core asanti-cancer drug carriers. European Polymer Journal, 2019, 120:109271
  4. Krasowska D, Iraci N, Santi C, Drabowicz J, Cieslak M, Kaźmierczak-Barańska J, Palomba M, Królewska-Golińska K, Magiera J, Sancineto L. Diselenides and Benzisoselenazolones as Antiproliferative Agents and Glutathione-S-Transferase Inhibitors. 2019, 11;24(16). pii: E2914
  5. Królewska-Golińska K, Cieślak MJ, Sobczak M, Dolot R, Radzikowska-Cieciura E, Napiórkowska M, Wybrańska I, Nawrot B. Novel benzo[b]furans with anti-microtubule activity upregulate expression of apoptotic genes and arrest leukemia cells in G2/M phase. Anticancer Agents Med Chem. 2019, 19(3), 375-388
  6. Napiórkowska M, Cieślak M, Kaźmierczak-Barańska J, Królewska-Golińska K, Nawrot B. Synthesis of New Derivatives of Benzofuran as Potential Anticancer Agents. 2019 18;24(8). pii: E1529
  7. Richert M, Walczyk M, Cieślak MJ, Kaźmierczak-Barańska J, Królewska-Golińska K, Wrzeszcz G, Muzioł T, Biniak S. Synthesis, X-ray structure, physicochemical properties and anticancer activity of mer and fac Ru(III) triphenylphosphine complexes with a benzothiazole derivative as a co-ligand. Dalton Transactions 2019, 48: 10689–10702
  8. Stolarczyk M, Bryndal I, Matera-Witkiewicz A, Lis T, Królewska-Golińska K, Cieślak M, Kaźmierczak-Barańska J, Cieplik J. Synthesis, crystal structure and cytotoxic activity of novel 5-methyl-4-thiopyrimidine derivatives. Acta Crystallogr C Struct Chem. 2018, 1;74(Pt 10):1138-1145
  9. Pejovic A, Drabowicz J, Cieslak M, Kazmierczak-Baranska J, Krolewska-Golińska K. Synthesis, characterization and anticancer activity of novel ferrocene containing quinolinones: 1-Allyl-2-ferrocenyl-2,3-dihydroquinolin- 4(1H)-ones and 1-allyl-2-ferrocenylquinolin-4(1H)-ones. Journal of Organometallic Chemistry 2018, 873: 78-85
  10. Kaczmarek R., Korczyński D., Królewska-Golińska, K. A. Wheeler, F. A. Chavez, R. Dembinski. Organometallic nucleosides:  Synthesis and Biological Evaluation of Substituted Dicobalt Hexacarbonyl 2′-Deoxy-5-oxopropynyluridines. ChemistryOpen 2018, 18(3): 237-247
  11. Skoczynska A., Małecka M., Cieslak M., Kazmierczak-Baranska J., Krolewska K., Budzisz E. Synthesis, structural analysis, redox properties and in vitro antitumor evaluation of half-sandwich complexes of Ru(II) with aminocoumarins. Polyhedron 2017, 127: 307–314
  12. Sobiesiak M., Cieślak M., Królewska K., Kaźmierczak-Barańska J., Pasternak B., Budzisz E. Thiosemicarbazone-derived copper(II), cobalt(II) and nickel(II) complexes as potential anticancer agents : nuclease activity, cytotoxicity and apoptosis studies. New J. Chem. 2016, 40(11): 9761-9767
  13. Królewska-Golińska K. Mechanizmy regulacji apoptozy. Rozdział w podręczniku pod redakcją H. Koroniaka I J. Barciszewskiego “Na pograniczu chemii I biologii” 2016, Tom XXXVI; 31-62
  14. Kuran B., Napiórkowska M., Kossakowski J., Cieślak M., Kazmierczak-Barańska J., Królewska K., Nawrot B. New, substituted derivatives of dicarboximides and their cytotoxic properties. Anti-Cancer Agents in Med. Chem. 2016, 16(7): 852-864
  15. Żurawiński R., Mikołajczyk M., Cieślak M., Królewska K., Kaźmierczak-Barańska J. Synthesis and in vitro cytotoxicity of cross-conjugated prostaglandin A and J series and their hydroxy derivatives. Biomol Chem. 2015, 13(25):7000-7012
  16. Napiorkowska M., Cieslak M., Kazmierczak-Baranska J., Krolewska K., Czapla A., Kuran B. Synthesis and preliminary studies of biological activity of amino derivatives of 4-azatricyclo-[5.2.1.0(2,6)]dec-8-ene-3,5-dione with silicon in the structure. Heterocyclic Commun., 2015, 21: 19-24
  17. Lodyga-Chruscinska E, Symonowicz M, Sykula A, Bujacz A, Garribba E, Rowinska-Zyrek M, Oldziej S, Klewicka E, Janicka M, Krolewska K, Cieslak M, Brodowska K, Chruscinski L. Chelating ability and biological activity of hesperetin Schiff base. Inorg Biochem. 2015, 143:34-47
  18. Królewska K., Cieślak M., Kuran B., Krawiecka B., Kossakowski J., Wybrańska I., Nawrot B. New benzo[b]furane and dicarboximide derivatives with anticancer activity- studies on the mechanism of action in human cells. FEBS Journal 2014, 281: 489-48
  19. Krawiecka, Kuran B., Kossakowski J., Cieślak M., Kaźmierczak-Barańska J., Królewska K., Nawrot B. Synthesis and cytotoxic properties of halogen and aryl-heteroarylpiperazinyl derivatives of benzofurans. Anti-Cancer Agent in Med. Chem 2014, 15(1):115-21
  20. Baraniak J., Pietkiewicz A., Kaczmarek R., Radzikowska E., Kulik K., Królewska K., Cieslak M., Krakowiak A., Nawrot B. N-Acyl-phosphoramidates as potential novel form of gemcitabine prodrugs. Med. Chem. 2014, 1; 22(7): 2133-2140
  21. Kuran B., Kossakowski J., Cieślak M., Kaźmierczak-Barańska J., Królewska K., Cyrański M., Stępień D., Krawiecka M. Synthesis and biological activity of novel series of heterocyclic compounds containing succinimide moiety. Heterocyclic Commun. 2013, 19(4): 287296
  22. Krawiecka M., Kuran B., Kossakowski J., Kierzkowska M., Młynarczyk G., Cieślak M., Kaźmierczak-Barańska J., Królewska K., Dobrowolski M. A. Synthesis and biological activity of novel series of 1,3-benzoxazol-2(3h)-one derivatives. Pol. Pharm. 2013, 70(2): 245-253
  23. Krawiecka M., Kuran B., Kossakowski J., Kierzkowska M., Młynarczyk G., Kaźmierczak-Barańska J., Królewska K., Cieślak M. Synthesis and biological activity of 6-substituted 5-acetyl-4,7-dimethoxybenzofuran derivatives. Heterocyclic Commun., 2013, 19(4): 281286
  24. Barszcz B., Masternak J., Hodorowicz M., Matczak-Jon E., Jabłonska-Wawrzycka A., Stadnicka K., Zienkiewicz M., Królewska K., Kaźmierczak-Barańska J. Synthesis, crystal structure and NMR investigation of novel Ca(II) complexes with heterocyclic alcohol, aldehyde and carboxylate ligands. Evaluation of Ca(II) and Cd(II) analogues for anticancer activity. Inorganica Chimica Acta 2012, 399: 85–94
  25. Kuran B., Krawiecka M., Kossakowski J., Pindel Ł., Młynarczyk G., Cieślak M., Kaźmierczak-Barańska J., Królewska K. Synthesis and biological activity of a novel series of 6,7-dimethoxyquinazoline-2,4(1H,3H)-dione derivatives. Pol. Pharm. 2012, 69(1): 145-14
  26. Piotrowska D.G., Cieślak M., Królewska K, Wróblewski A.E. Design, synthesis and cytotoxicity of a new series of isoxazolidines derived from substituted chalcones. J. Med Chem. 2011, 46(4): 1382-1392
  27. Piotrowska D.G., Cieślak M., Królewska K, Wróblewski A.E. Design, synthesis and cytotoxicity of a new series of isoxazolidine based nucleoside Arch. Pharm. (Weinheim). 2011, 344(5): 301-310
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