Medicinal Chemistry and Bioactive Natural Compounds
Head: Milan Urban
Olomouc node
HOME INSTITUTION
Faculty of Medicine PU in Olomouc
RESEARCH PROGRAMME(S)
RP 1 - Molecular basis of cancer and molecular targets
RP 2 - Research and development of anticancer pharmaceuticals and therapeutic methods
Nature is the best designer of medicines.
- Mission: Search for analogues of natural substances relevant for the diagnosis and treatment of cancer.
- Vision: Using small molecules to selectively target biological processes in tumours.
The research group is focused on the study of natural substances and their analogues, especially triterpenoids with anticancer activity. Natural substances are an almost inexhaustible source of new, structurally variable molecular entities with a wide range of biological effects. The main advantage of using triterpenes as therapeutics is (often) low toxicity and high biological activity, which is desirable for drug development. Since triterpenoids often target important proteins that play a role in many cellular pathways and show a different mechanism of action than currently used drugs, we expect them to become an important tool to overcome drug resistance.
SELECTED PUBLICATIONS
- Kazakova A, Frydrych I, Jakubcová N, Pokorný J, Lišková B, Gurská S, Hajdúch M, Džubák P, Urban M. Novel triterpenoid pyrones, phthalimides and phthalates are selectively cytotoxic in CCRF-CEM cancer cells – Synthesis, potency, and mitochondrial mechanism of action. Eur J Med Chem. 2024 Apr 5;269:116336. DOI: 10.1016/j.ejmech.2024.116336
- Hodoň J, Frydrych I, Trhlíková Z, Pokorný J, Borková L, Benická S, Vlk M, Lišková B, Kubíčková A, Medvedíková M, Pisár M, Šarek J, Das V, Ligasová A, Koberna K, Džubák P, Hajdúch M, Urban M. Triterpenoid pyrazines and pyridines – synthesis, cytotoxicity, mechanism of action, preparation of prodrugs. Eur J Med Chem. 2022 Dec 5;243:114777. DOI: 10.1016/j.ejmech.2022.114777
- Borková L, Frydrych I, Vránová B, Jakubcová N, Lišková B, Gurská S, Džubák P, Pavliš P, Hajdúch M, Urban M. Lupane derivatives containing various aryl substituents in the position 3 have selective cytostatic effect in leukemic cancer cells including resistant phenotypes. Eur J Med Chem. 2022 Dec 15;244:114850. DOI: 10.1016/j.ejmech.2022.114850
- Pokorný J, Olejníková D, Frydrych I, Lišková B, Gurská S, Benická S, Šarek J, Kotulová J, Hajdúch M, Džubák P, Urban M. Substituted dienes prepared from betulinic acid – Synthesis, cytotoxicity, mechanism of action, and pharmacological parameters. Eur J Med Chem. 2021 Nov 15;224:113706. DOI: 10.1016/j.ejmech.2021.113706
- Borková L, Frydrych I, Jakubcová N, Adámek R, Lišková B, Gurská S, Medvedíková M, Hajdúch M, Urban M. Synthesis and biological evaluation of triterpenoid thiazoles derived from betulonic acid, dihydrobetulonic acid, and ursonic acid. Eur J Med Chem. 2020 Jan 1;185:111806. DOI: 10.1016/j.ejmech.2019.111806
COLLABORATION WITHIN THE NICR
Marián Hajdúch
(Olomouc node, Faculty of Medicine PU in Olomouc)
Petr Džubák
(Olomouc node, Faculty of Medicine PU in Olomouc)
Tomáš Etrych
(Prague node, Institute of Macromolecular Chemistry of the Czech Academy of Sciences)
Vladimír Kryštof
(Olomouc node, Faculty of Medicine PU in Olomouc)
SPECIALIZED EXPERTISE AND TECHNOLOGY
Targeted organic synthesis
Purification, isolation, characterization of organic molecules
Preparation of conjugates (fluorescent, affinity, etc.) for biological applications
Preparation of prodrugs, modification of pharmacological profile of molecules
COLLABORATION WITH LARGE RESEARCH INFRASTRUCTURES AND RESEARCH CENTRES
Institute of Molecular and Translational Medicine IMTM