2017 Ing. University of chemistry and technology, Prague (Organic chemistry)
present PhD University of chemistry and technology, Prague (Organic chemistry)
RESEARCH, TEACHING, or OTHER INTERESTS
Organic Chemistry, Chemistry
14
Scopus Publications
Scopus Publications
Hydrogel modified nanofibers for the delivery of doxorubicin and high dose of curcumin Petr Dytrych, Radoslav Janostiak, Stela Bajusová, Zdeněk Kejík, Nikita Abramenko, Kateřina Kučnirová, Ameneh Tatar, Adéla Paulusová, Daniela Popelkova, David Liebl, Robert Kaplánek, Jan Hajduch, David Hoskovec, Pavel Martásek, Milan Jakubek Journal of Drug Delivery Science and Technology, 2026 The combination of cytostatics (e.g., doxorubicin) with natural compounds such as curcumin can be an effective strategy in treating malignancies. Curcumin enhances doxorubicin's anticancer effects, but curcumin solubility is very low. Nanofibers are promising drug delivery systems, typically loaded with drugs (into them) during electrospinning. However, modifying their surface with hydrogels containing anticancer agents may increase therapeutic efficacy. Therefore, the modification of nanostrips with curcumin and doxorubicin was a part of this study. The surface of commercially available nanostrips was modified with hydrogels and HP-β-CD containing a doxorubicin and curcumin. Upon incubation of these modified nanostrips in a buffer solution, the majority of the loaded agents were released, achieving concentrations of 190 μM for curcumin and 15 μM for doxorubicin. These concentrations were sometimes higher than the effective doses represented by the IC 50 values for colorectal cancer cell lines (DLD1, HCT116, LS147, and SW620) and pancreatic cancer cell lines (PANC1, Patu8902, AsPC1, and BxPC3). In addition, a combined dose of 27 μM curcumin and 1 μM doxorubicin resulted in the disintegration of primary human colorectal carcinoma organoids. • New methodology for the surface modification of nanofiber by drugs is presented. • Modified nanofiber was characterized by SEM and FTIR. • In the PBS (10 ml) concentration released curcumin and doxorubicin was 190 and 15 μM. • Effective dose against colorectal and pancreatic cancer cells was 27 and 1 μM. • Its application disintegrates primary colorectal carcinoma organoids.
Synthesis of Substituted Tetrafluorocyclobutenes and Their Ring-Opening Metathesis/Ring-Closing Metathesis to Dihydrofurans Bearing a Tetrafluoroethylene Unit Kateřina Kučnirová, Jaroslav Kvíčala, Josef Cvačka, Markéta Rybáčková ACS Omega, 2026 High Resolution Image Download MS PowerPoint Slide We report the synthesis of a series of pentafluoro- and tetrafluorocyclobutenes containing alkylthio, phenylthio, alkoxy, phenoxy, and benzyloxy groups via reactions of perfluorocyclobutene with S - and O -nucleophiles. Although these substrates do not undergo ring-opening cross-metathesis with terminal alkenes, the synthesis of dihydrofurans bearing a tetrafluoroethylene unit in the side chain was achieved through a one-pot cascade reaction involving ring-opening and subsequent ring-closing metatheses of alkenyloxy tetrafluorocyclobutenes using the Hoveyda–Grubbs second-generation precatalyst.
Novel structure motif for the selective inhibition of TET1 protein based on perimidines Zdeněk Kejík, Robert Kaplánek, Nikita Abramenko, Frédéric Vellieux, Kateřina Veselá, Petr Babula, Michal Masařík, Jan Ulrich, Kateřina Kučnirová, Jan Hajduch, Pavel Martásek, Milan Jakubek Journal of Molecular Structure, 2026 The targeting of epigenetic factors, particularly TET proteins (ten-eleven translocation methylcytosine dioxygenases), has emerged as a significant focus in medicinal and biological research. Recent findings indicate that iron chelators possess substantial potential for inhibiting TET activity. In this study, we synthesized two 2-(hetero)aryl-1H-perimidines (perimidine 1 and 2) with iron(II) binding properties. The results show that these derivatives, particularly 2, exhibit notable inhibitory activity and selectivity for the TET1 protein, with an IC50 value of 1.02 µM, in contrast to TET2, which has an IC50 value of 13.23 µM.
Interaction of Selected Anthracycline and Tetracycline Chemotherapeutics with Poly(I:C) Molecules Markéta Skaličková, Nikita Abramenko, Tatsiana Charnavets, Frédéric Vellieux, Jindřiška Leischner Fialová, Kateřina Kučnirová, Zdeněk Kejík, Michal Masařík, Pavel Martásek, Karel Pacak, Tomáš Pacák, Milan Jakubek ACS Omega, 2025 High Resolution Image Download MS PowerPoint Slide Despite the natural ability of the immune system to recognize cancer and, in some patients, even to eliminate it, cancer cells have acquired numerous evading mechanisms. With the increasing knowledge and focus shifting from targeting rapidly proliferating cells with chemotherapy to modulating the immune system, there have been recent efforts to integrate (e.g., simultaneously or sequentially) various therapeutic approaches. Combining the oncolytic activity of some chemotherapeutics with immunostimulatory molecules, so-called chemoimmunotherapy, is an attractive strategy. An example of such an immunostimulatory molecule is polyinosinic:polycytidylic acid [Poly(I:C)], a synthetic analogue of double-stranded RNA characterized by rapid nuclease degradation hampering its biological activity. This study investigated the possible interactions of tetracycline and anthracycline chemotherapeutics with different commercial Poly(I:C) molecules and protection against nuclease degradation. Fluorescence spectroscopy and circular dichroism revealed an interaction of all of the selected chemotherapeutics with Poly(I:C)s and the ability of doxycycline and minocycline to prolong the resistance to RNase cleavage, respectively. The partial protection was observed in vitro as well.
Ruthenium-enhanced curcumin derivatives target tumor growth and cancer-related inflammation in head and neck cancer models Kateřina Veselá, Ameneh Tatar, Zdeněk Kejík, Nikita Abramenko, Robert Kaplánek, Petr Babula, Kateřina Kučnirová, Jan Hajduch, Pavel Martásek, Milan Jakubek Frontiers in Oncology, 2025 Introduction Head and neck cancers (HNC) remain a significant clinical challenge, particularly due to their association with chronic inflammation triggered by tobacco carcinogens and human papillomavirus (HPV) infection. Persistent activation of proinflammatory and proangiogenic pathways, including nuclear factor kappa B (NF-kB), interleukin 6 (IL-6), and interleukin 8 (IL-8), plays a crucial role in tumor progression. Methods In this study, we synthetized ruthenium-enhanced curcumin derivatives (complexes 3 and 4) and study their anti-inflammatory and anticancer properties by using HNC cell lines. Results Complex 3 demonstrated potent cytotoxic and antiproliferative effects across both HPV-negative and HPV- positive HNC cell lines, while complex 4 showed selectivity toward oral squamous cell carcinoma (OSCC). Both complexes exhibited cytostatic and migrastatic activities. Importantly, treatment with these complexes significantly suppressed NF-kB activity and reduced IL-6 and IL-8 levels more effectively than native curcumin. Discussion These findings highlight their potential not only as stand-alone therapeutic agents but also as adjuvants in combination therapies for HNC.
Cyanine dyes in the mitochondria-targeting photodynamic and photothermal therapy Zdeněk Kejík, Jan Hajduch, Nikita Abramenko, Frédéric Vellieux, Kateřina Veselá, Jindřiška Leischner Fialová, Kateřina Petrláková, Kateřina Kučnirová, Robert Kaplánek, Ameneh Tatar, Markéta Skaličková, Michal Masařík, Petr Babula, Petr Dytrych, David Hoskovec, Pavel Martásek, Milan Jakubek Communications Chemistry, 2024 Mitochondrial dysregulation plays a significant role in the carcinogenesis. On the other hand, its destabilization strongly represses the viability and metastatic potential of cancer cells. Photodynamic and photothermal therapies (PDT and PTT) target mitochondria effectively, providing innovative and non-invasive anticancer therapeutic modalities. Cyanine dyes, with strong mitochondrial selectivity, show significant potential in enhancing PDT and PTT. The potential and limitations of cyanine dyes for mitochondrial PDT and PTT are discussed, along with their applications in combination therapies, theranostic techniques, and optimal delivery systems. Additionally, novel approaches for sonodynamic therapy using photoactive cyanine dyes are presented, highlighting advances in cancer treatment.
Quaternary ammonium fluorides and difluorosilicates as nucleophilic fluorination reagents Michal Trojan, Kateřina Kučnirová, Šárka Bouzková, Josef Cvačka, Jan Čejka, Gašper Tavčar, Markéta Rybáčková, Jaroslav Kvíčala Organic and Biomolecular Chemistry, 2023 Fluorination reactivity and selectivity of TBAT and four new nucleophilic fluorination reagents were better than those of TBAF, TASF and other quaternary ammonium fluorides.
TET protein inhibitors: Potential and limitations Robert Kaplánek, Zdeněk Kejík, Jan Hajduch, Kateřina Veselá, Kateřina Kučnirová, Markéta Skaličková, Anna Venhauerová, Božena Hosnedlová, Róbert Hromádka, Petr Dytrych, Petr Novotný, Nikita Abramenko, Veronika Antonyová, David Hoskovec, Petr Babula, Michal Masařík, Pavel Martásek, Milan Jakubek Biomedicine and Pharmacotherapy, 2023 TET proteins (methylcytosine dioxygenases) play an important role in the regulation of gene expression. Dysregulation of their activity is associated with many serious pathogenic states such as oncological diseases. Regulation of their activity by specific inhibitors could represent a promising therapeutic strategy. Therefore, this review describes various types of TET protein inhibitors in terms of their inhibitory mechanism and possible applicability. The potential and possible limitations of this approach are thoroughly discussed in the context of TET protein functionality in living systems. Furthermore, possible therapeutic strategies based on the inhibition of TET proteins are presented and evaluated, especially in the field of oncological diseases.
Influence of Isomeric Composition and Sample Handling on the Liquid Density of Hydrofluorethers Measured by Vibrating Tube Densimeter at 0.1 MPa Olga Prokopová, Aleš Blahut, Jan Hajduch, Kateřina Kučnirová, Miroslav Čenský, Ali Aminian, Markus Richter, Václav Vinš International Journal of Thermophysics, 2023 Hydrofluoroethers (HFEs) represent a new family of promising engineering fluids suitable for technical cleaning and cooling of electronic and magnetic devices or as admixtures in refrigerant blends. Here, we report accurate data for the liquid density at 0.1 MPa and temperatures from $$273.15\\,\\text{K}$$ 273.15 K to $$343.15\\,\\text{K}$$ 343.15 K for a series of five HFEs, namely, HFE-7000, HFE-7100, HFE-7200, HFE-7300, and HFE-7500. A highly sensitive vibrating tube densimeter with a borosilicate glass U-tube calibrated according to the procedure by Prokopová et al. (J Chem Thermodyn 173:106855, 2022) provided density data with an expanded uncertainty ($$k=2$$ k = 2 ) of $$0.13\\,\\text{kg}\\cdot \\text{m}^{-3}$$ 0.13 kg · m - 3 . Influences such as sample degassing, water content, or sample temperature before its dosing into the densimeter are discussed. Thanks to the high sensitivity of the used densimeter, an unexpected shift in the density of different HFE-7100 and HFE-7200 liquid samples was detected. Unlike other HFEs, HFE-7100 and HFE-7200 are mixtures of two hardly separable isomers, which were so far considered having identical thermophysical properties. Utilizing nuclear magnetic resonance spectroscopy, the ratio of n-isomer and iso-isomer was inspected for various liquid samples. In the range of iso-isomer mole fraction from 0.61 to 0.77, the new measurements revealed density differences of more than $$5\\,\\text{kg}\\cdot \\text{m}^{-3}$$ 5 kg · m - 3 in case of HFE-7100 and of about $$3\\,\\text{kg}\\cdot \\text{m}^{-3}$$ 3 kg · m - 3 in case of HFE-7200. Consequently, for some applications, the properties of different HFE isomers cannot be considered identical. The Rackett-type correlation for the saturated liquid density was fitted using the new and the literature data.
Therapeutic potential and limitations of curcumin as antimetastatic agent Petr Dytrych, Zdeněk Kejík, Jan Hajduch, Robert Kaplánek, Kateřina Veselá, Kateřina Kučnirová, Markéta Skaličková, Anna Venhauerová, David Hoskovec, Pavel Martásek, Milan Jakubek Biomedicine and Pharmacotherapy, 2023 Treatment of metastatic cancer is one of the biggest challenges in anticancer therapy. Curcumin is interesting nature polyphenolic compound with unique biological and medicinal effects, including repression of metastases. High impact studies imply that curcumin can modulate the immune system, independently target various metastatic signalling pathways, and repress migration and invasiveness of cancer cells. This review discusses the potential of curcumin as an antimetastatic agent and describes potential mechanisms of its antimetastatic activity. In addition, possible strategies (curcumin formulation, optimization of the method of administration and modification of its structure motif) to overcome its limitation such as low solubility and bioactivity are also presented. These strategies are discussed in the context of clinical trials and relevant biological studies.
