Iuliia Melnikova
@faf.cuni.cz
Faculty of Pharmacy in Hradec Kralove, Department of Organic and Bioorganic Chemistry
Charles University, Faculty of Pharmacy in Hradec Kralove
EDUCATION
Saint-Petersburg State University of Industrial Technologies and Design: St. Petersburg, RU
2014-10-01 to 2018-09-30 | PhD in Organic Chemistry (Applied Chemistry and Ecology)
St. Petersburg State Technological Institute (technical university) : St. Petersburg, RU
2009-09-01 to 2014-06-20 | Engineer (Chemical and Biotechnology)
RESEARCH, TEACHING, or OTHER INTERESTS
Organic Chemistry, Physical and Theoretical Chemistry
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Veronika Keresteš, Jan Kubeš, Lenka Applová, Petra Kollárová, Olga Lenčová-Popelová, Iuliia Melnikova, Galina Karabanovich, Mushtaq M Khazeem, Hana Bavlovič-Piskáčková, Petra Štěrbová-Kovaříková,et al.
Oxford University Press (OUP)
Abstract Anthracyclines, such as doxorubicin (adriamycin), daunorubicin, or epirubicin, rank among the most effective agents in classical anticancer chemotherapy. However, cardiotoxicity remains the main limitation of their clinical use. Topoisomerase IIβ has recently been identified as a plausible target of anthracyclines in cardiomyocytes. We examined the putative topoisomerase IIβ selective agent XK469 as a potential cardioprotective and designed several new analogs. In our experiments, XK469 inhibited both topoisomerase isoforms (α and β) and did not induce topoisomerase II covalent complexes in isolated cardiomyocytes and HL-60, but induced proteasomal degradation of topoisomerase II in these cell types. The cardioprotective potential of XK469 was studied on rat neonatal cardiomyocytes, where dexrazoxane (ICRF-187), the only clinically approved cardioprotective, was effective. Initially, XK469 prevented daunorubicin-induced toxicity and p53 phosphorylation in cardiomyocytes. However, it only partially prevented the phosphorylation of H2AX and did not affect DNA damage measured by Comet Assay. It also did not compromise the daunorubicin antiproliferative effect in HL-60 leukemic cells. When administered to rabbits to evaluate its cardioprotective potential in vivo, XK469 failed to prevent the daunorubicin-induced cardiac toxicity in either acute or chronic settings. In the following in vitro analysis, we found that prolonged and continuous exposure of rat neonatal cardiomyocytes to XK469 led to significant toxicity. In conclusion, this study provides important evidence on the effects of XK469 and its combination with daunorubicin in clinically relevant doses in cardiomyocytes. Despite its promising characteristics, long-term treatments and in vivo experiments have not confirmed its cardioprotective potential.
Paulina Hatokova, Vit Sestak, Hana Bavlovic Piskackova, Iuliia Melnikova, Jaroslav Roh, and Petra Sterbova-Kovarikova
Elsevier BV
Hana Bavlovič Piskáčková, Hana Jansová, Jan Kubeš, Galina Karabanovich, Nela Váňová, Petra Kollárová-Brázdová, Iuliia Melnikova, Anna Jirkovská, Olga Lenčová-Popelová, Jaroslav Chládek,et al.
Springer Science and Business Media LLC
AbstractThe bisdioxopiperazine topoisomerase IIβ inhibitor ICRF-193 has been previously identified as a more potent analog of dexrazoxane (ICRF-187), a drug used in clinical practice against anthracycline cardiotoxicity. However, the poor aqueous solubility of ICRF-193 has precluded its further in vivo development as a cardioprotective agent. To overcome this issue, water-soluble prodrugs of ICRF-193 were prepared, their abilities to release ICRF-193 were investigated using a novel UHPLC-MS/MS assay, and their cytoprotective effects against anthracycline cardiotoxicity were tested in vitro in neonatal ventricular cardiomyocytes (NVCMs). Based on the obtained results, the bis(2-aminoacetoxymethyl)-type prodrug GK-667 was selected for advanced investigations due to its straightforward synthesis, sufficient solubility, low cytotoxicity and favorable ICRF-193 release. Upon administration of GK-667 to NVCMs, the released ICRF-193 penetrated well into the cells, reached sufficient intracellular concentrations and provided effective cytoprotection against anthracycline toxicity. The pharmacokinetics of the prodrug, ICRF-193 and its rings-opened metabolite was estimated in vivo after administration of GK-667 to rabbits. The plasma concentrations of ICRF-193 reached were found to be adequate to achieve cardioprotective effects in vivo. Hence, GK-667 was demonstrated to be a pharmaceutically acceptable prodrug of ICRF-193 and a promising drug candidate for further evaluation as a potential cardioprotectant against chronic anthracycline toxicity.
Anna Jirkovská, Galina Karabanovich, Jan Kubeš, Veronika Skalická, Iuliia Melnikova, Jan Korábečný, Tomáš Kučera, Eduard Jirkovský, Lucie Nováková, Hana Bavlovič Piskáčková,et al.
American Chemical Society (ACS)
Cardioprotective activity of dexrazoxane (ICRF-187), the only clinically approved drug against anthracycline-induced cardiotoxicity, has traditionally been attributed to its iron-chelating metabolite. However, recent experimental evidence suggested that the inhibition and/or depletion of topoisomerase IIβ (TOP2B) by dexrazoxane could be cardioprotective. Hence, we evaluated a series of dexrazoxane analogues and found that their cardioprotective activity strongly correlated with their interaction with TOP2B in cardiomyocytes, but was independent of their iron chelation ability. Very tight structure-activity relationships were demonstrated on stereoisomeric forms of 4,4'-(butane-2,3-diyl)bis(piperazine-2,6-dione). In contrast to its rac-form 12, meso-derivative 11 (ICRF-193) showed a favorable binding mode to topoisomerase II in silico, inhibited and depleted TOP2B in cardiomyocytes more efficiently than dexrazoxane, and showed the highest cardioprotective efficiency. Importantly, the observed ICRF-193 cardioprotection did not interfere with the antiproliferative activity of anthracycline. Hence, this study identifies ICRF-193 as the new lead compound in the development of efficient cardioprotective agents.
Iuliia Melnikova, Jaroslav Roh, Jiří Kuneš, Tatiana Artamonova, Yuri Zevatskii, and Leonid Myznikov
Elsevier BV
RECENT SCHOLAR PUBLICATIONS
MOST CITED SCHOLAR PUBLICATIONS
Publications
1. Mel’nikova Yu. V., Myznikov L. V., Dogadina A. V., Svintsitskaya N. I., Reactions of dimethyl 2-chloroethynylphosphonate with 1-substituted 5-oxo-1H-1,2,3,4-tetrazoles. Russian Journal of General Chemistry. 2014; 84 (11): 2160-2167.
2. Mel’nikova Yu. V., Lyakhov A. S., Ivashkevich L. S., Artamonova T. V., Novoselov N. P., Zevatskii Yu. E., Myznikov L. V. The Bargellini Reaction in a Series of Heterocyclic Thiols. Russian Journal of General Chemistry. 2016; 86 (2): 312-316. (IF2016 = 0.553)
3. Mel’nikova Yu. V., Myznikov L. V., Artamonova T. V., Vorona S. V., Novoselov N. P., Zevatskii Yu. E. The Bargellini Reaction. Vestnik of St. Petersburg State University of Technology and Design. Series 1. Natural and technical science (in rus.). 2016; 2: 57-64.
4. Melnikova Yu. V., Skripnikova T. A., Lysova S.S., Myznikov L. V., Zevatskii Yu. E. Constants of protolytic equilibria of 1-substituted tetrazole-5-thioles in aqueous solutions. News of the St. Petersburg State Technological Institute (Technical University) (in rus.). 2017; 41 (67): 67-70.
5. Ivanov V. A., Novoselov N. P., Michaylovskaya A. P., Melnikova Iu. V. Organic chemistry. Course of lectures [Electronic resource]: a tutorial. 2017: 221.
6. Myznikov L. V., Melnikova Yu. V., Baichurin R. I., Artamonova T. V., Zevatskii Yu. E. Pd2+-Catalyzed Addition of 1-Substituted Tetrazole-5-thiols to Terminal Acetylenes in Acid Medium. Russian Journal of General Chemistry. 2018; 88 (2): 216-220.
INDUSTRY EXPERIENCE
NOVBYTCHIM Company: St. Petersburg, RU
2014-11-01 to 2018-10-31 | Engineer