Mgr. Jindřich Karban, Ph.D.

Position: 
Scientist

Phone: 
+420 220 390 252, +420 220 390 264
E-mail: 
karbanaticpf [dot] cas [dot] cz

Address: 
Rozvojová 135/1, 165 02 Praha-Lysolaje, Česká republika
Room number: 
99
Workgroup: 
Department of Bioorganic Compounds and Nanocomposites

Research interests:

  • fluorinated monosaccharides
  • antitumour carbohydrate – metallocene conjugates
  • aziridine derivatives of aldohexoses

including mechanistic aspects of the synthesis and reactivity of these carbohydrate analogues, conformational analysis on the basis of their crystallographic and spectroscopic properties, and application in medicinal chemistry and glycobiology

Fluorinated carbohydrates continue to attract attention of synthetic chemists and glycobiologists. Introduction of fluorine into carbohydrates modifies their stereoelectronic, lipophilic, steric, and hydrogen-bonding properties. These modifications in turn lead to alterations of their interactions with proteins and other biomolecules or to a greater metabolic stability in comparison with the parent carbohydrates. Fluorinated sugars are used, for example, as probes in studies of enzym – carbohydrate and lectin – carbohydrate interactions, inhibitors of carbohydrate processing enzymes, chemical agents used for modification of the cellular glycome, model compounds for the study of fluorine hydrogen bonding, or components of anticancer vaccines.

Publications:

  • Stereoselectivity in Glycosylation with Deoxofluorinated Glucosazide and Galactosazide Thiodonors, Kurfiřt, M.; Červenková Št’astná, L.; Dračínský, M.; Müllerová, M.; Hamala, V.; Cuřínová, P.; Karban, J.,  J. Org. Chem. 2019, 84, 6405-6431. https://doi.org/10.1021/acs.joc.9b00705

  • Synthesis and in Vitro Cytotoxicity of Acetylated 3-Fluoro, 4-Fluoro and 3,4-Difluoro Analogs of D-glucosamine and D-galactosamine, Horník Š.; Červenková Šťastná L.; Cuřínová P.; Sýkora J.; Káňová K.; Hrstka R.; Císařová I.; Dračínský M.; Karban J. Beilstein J. Org. Chem. 2016, 12, 750-759. http://dx.doi.org/10.3762/bjoc.12.75

  • A Convenient Route to Peracetylated 3-Deoxy-3-fluoro Analogues of D-Glucosamine and D-Galactosamine from a Černý Epoxide, Karban, J.; Horník, t.; Červenková Šťastná, L.; Sýkora, J. Synlett 2014, 25, 1253-1256. http://dx.doi.org/10.1055%2Fs-0033-1341187                                                                                                                                                                                                                                                            
  • Skeletal rearrangements resulting from reactions of 1,6:2,3- and 1,6:3,4-dianhydro-β-D-hexopyranoses with diethylaminosulphur trifluoride, Karban, J.; Císařová, I.; Strašák, T.; Červenková Šťastná, L.; Sýkora, J. Org. Biomol. Chem. 2012, 10, 94-403. http://dx.doi.org/10.1039%2FC1OB06336G                                                                                                                                                                                                                                                                                                  
  • Synthesis of All Configurational Isomers of 1,6-Anhydro-2,3,4-trideoxy-2,3-epimino-4-fluoro-β-D-hexopyranoses, Karban, J.; Sýkora, J.; Kroutil, J.; Císařová, I.; Padělková, Z.; Buděšínský, M. J. Org. Chem. 2010, 75, 3443-3446. http://dx.doi.org/10.1021%2Fjo1000912

Carbohydrate – metallocene conjugates. Metallocenes are organometallic compounds characterized by a transition metal central atom (M) bound to cyclopentadienide (Cp-/C5H5-) ligands, the general formula of metallocenes being Cp2M. Titanocene dichloride was among the first non-platinum organometallics investigated as promising anticancer agents. Although its clinical trials were stopped because of low efficacy and other drawbacks, the last two decades have witnessed renewed research interest in anticancer metallocenes. We have started a programme aimed at improving cytotoxic activity and pharmacological properties of metallocenes by their conjugation to carbohydrates, iminosugars and selected heterocycles. Carbohydrates and iminosugars have typicaly 3 - 6 functional groups that can be modified to ameliorate cytotoxic profile, bioavailability, solubility, biocompatibility, and hydrophobic/hydrophilic balance of the resulting metallocene-carbohydrate conjugate. Recently, we have extended this concept to other organometallic compounds, such as arene ruthenium cationic complexes.

Publications:

  • Harmless glucose-modified ruthenium complexes suppressing cell migration of highly invasive cancer cell lines. Lamač, M., Horáček, M., Červenková Šťastná, L., Karban, J., Sommerová, L., Skoupilová, H., Hrstka, R., Pinkas, J.: Appl. Organomet. Chem. In Press. https://doi.org/10.1002/aoc.5318
  • Ferrocenes as new anticancer drug candidates: Determination of the mechanism of action. Skoupilova, H., Bartosik, M., Sommerova, L., Pinkas, J., Vaculovic, T., Kanicky, V., Karban, J., Hrstka, R.: Eur. J. Pharmacol. 2020, 867, 172825. https://doi.org/10.1016/j.ejphar.2019.172825
  •  Improving Cytotoxic Properties of Ferrocenes by Incorporation of Saturated N-heterocycles. Hodik T., Lamac M., Cervenkova Stastna L., Curinova P., Karban J., Skoupilova H., Hrstka R., Cisarova I., Gyepes R., Pinkas J.: J. Organomet. Chem. 2017, 846, 141-151. https://doi.org/10.1016/j.jorganchem.2017.06.005
  • Electrochemical Analysis of a Novel Ferrocene Derivative as a Potential Antitumor Drug, Bartošík, M; Koubková, L.; Karban, J.; Červenková Šťastná, L.; Hodík, T.; Lamač, M.; Pinkas, J.; Hrstka, R. Analyst 2015, 140, 5864-5867. http://pubs.rsc.org/en/Content/ArticleLanding/2015/AN/c5an00958h#!divAbstract
  • Evaluation of Cytotoxic Activity of Titanocene Difluorides and Determination of Their Mechanism of Action in Ovarian Cancer Cells, Koubková L., Vyzula R., Karban J., Pinkas J., Ondroušková E., Vojtěšek B., Hrstka, R. Invest. New Drugs 2015, 33, 1123-1132.  http://link.springer.com/article/10.1007%2Fs10637-015-0274-y
  • Titanocene Dihalides and Ferrocenes Bearing a Pendant α-D-Xylofuranos-5-yl or α-D-Ribofuranos-5-yl Moiety. Synthesis, Characterization, and Cytotoxic Activity, Hodík, T.; Lamač, M.; Červenková Šťastná, L.; Karban, J.; Koubková, L.; Hrstka, R.; Císařová, I.; Pinkas, J. Organometallics 2014, 33, 2059-2070. http://pubs.acs.org/doi/abs/10.1021/om500200r

Aziridine derivatives of aldohexoses Aziridines are versatile synthetic intermediates. Important for their utilization in this regard is the cleavage of the three-membered aziridine ring. Cleavage of N-tosylated aziridine ring annelated to a tetrahydropyrane ring of aldohexopyranoses affords interesting analogues of aminosugars which are difficult to prepare otherwise.  We studied regio- and stereoselectivity of aziridine ring cleavage fused to the tetrahydropyrane ring of 1,6-anhydro-β-D-hexopyranoses.

Publications:

         

                                                                                                      

List of papers published during last 4 years (journals and books only):