Ivanna Subtelna
@new.meduniv.lviv.ua
department of pharmaceutical, organic and bioorganic chemistry
Danylo Halutsky Lviv National Medical University
RESEARCH, TEACHING, or OTHER INTERESTS
Organic Chemistry, Pharmaceutical Science, Drug Discovery
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Jiri Rehulka, Ivanna Subtelna, Anna Kryshchyshyn‐Dylevych, Alina Cherniienko, Aleksandra Ivanova, Mariia Matveieva, Pavel Polishchuk, Sona Gurska, Marian Hajduch, Oleh Zagrijtschuk,et al.
Wiley
AbstractStudying the anticancer activity of 5‐arylidene‐2‐(4‐hydroxyphenyl)aminothiazol‐4(5H)‐ones towards cell lines of different cancer types allowed the identification of hit‐compounds inhibiting the growth of daunorubicin‐ (CEM‐DNR, IC50 = 0.32–1.28 µM) and paclitaxel‐resistant (K562‐TAX, IC50 = 0.21–1.23 µM) cell lines, with favorable therapeutic indexes. The studied compounds induced apoptosis and cellular proliferation in treated CCRF‐CEM cells. The hit compounds were shown to induce mitotic arrest by interacting with tubulin, inhibiting its polymerization by binding to the colchicine binding site.
A. P. Kryshchyshyn-Dylevych, I. Y. Subtelna, N. S. Finiuk, L. Radko, A. Pawełczyk, R. S. Stoika, and R. B. Lesyk
Institute of Molecular Biology and Genetics (NAS Ukraine)
Ivanna Subtelna, Anna Kryshchyshyn‐Dylevych, Ruochen Jia, Maryan Lelyukh, Anna Ringler, Stefan Kubicek, Oleh Zagrijtschuk, Robert Kralovics, and Roman Lesyk
Wiley
AbstractThe data on the pharmacology of 4‐thiazolidinones showed that 5‐ene‐2‐(imino)amino‐4‐thiazolidinones are likely to comprise one of the most promising groups of compounds possessing anticancer properties. A series of 5‐arylidene‐2‐(4‐hydroxyphenyl)aminothiazol‐4(5H)‐ones was designed, synthesized, and studied against 10 leukemia cell lines, including the HL‐60, Jurkat, K‐562, Dami, KBM‐7, and some Ba/F3 cell lines. The structure–activity relationship analysis shows that almost all tested 5‐arylidene‐2‐(4‐hydroxyphenyl)aminothiazol‐4(5H)‐ones were characterized by ІС50 values lower or comparable to that of the control drug chlorambucil. Among the tested compounds, (5Z)‐5‐(2‐methoxybenzylidene)‐ (12), (5Z)‐(2‐ethoxybenzylidene)‐ (21), (5Z)‐5‐(2‐benzyloxybenzylidene)‐ (25), and (5Z)‐5‐(2‐allyloxybenzylidene)‐2‐(4‐hydroxyphenylamino)thiazol‐4(5H)‐ones (28) possessed the highest antileukemic activity at submicromolar concentrations (ІС50 = 0.10–0.95 µM).
L. Kоbylinska, , D. Khylyuk, I. Subtelna, M. Kitsera, R. Lesyk, , , , and
National Academy of Sciences of Ukraine (Co. LTD Ukrinformnauka)
Synthetic 4-thiazolidinone derivatives have a broad range of pharmacologic activities. Thus, 4-thia-zolidinones are being investigated to create new molecules and develop active pharmaceutical substances for anticancer treatment. In our previous study, we investigated the pyrazoline-thiazolidinone-isatin conjugates, and determined that Les-3833 was the most active compound and might act through inhibition of ParP-, MaPK-, JnK-, bcl-2-, CDK1/cyclin b, and/or the caspase family. the aim of this research was to perform molecular docking studies to enable the construction of a pharmacophore model for the Les-3833 compound and investigate probable biological targets. Pharmacophore modeling software packages performed molecular docking studies of probable biological targets and enabled the construction of a pharmacophore model. Docking models of Les-3833 with 11 enzymes involved in apoptotic mechanisms were studied. Based on the pharmacophore modeling results for all 11 enzymes, Les-3833 is predicted to be most active in Chk-1, caspase-6, and caspase-8. Immunoblot analysis proved that the application of Les-3833 led to inhibition of ser345 phosphorylation, which is induced by etoposide, the most important modification responsible for Chk-1 activity. Taken together with the results of the docking studies, several mechanisms for the expression of antitumor activity by 4-thiazolidinones are suggested, and such multi-affinity is a characteristic feature of all these derivatives. the docking analysis confirmed the affinity of test compound Les-3833 for a topoisomerase II inhibitor and a high possibility of inhibitory interaction with Chk-1, caspase-6, and caspase-8.
Roman Lesyk, Danylo Kaminskyy, Ivanna Subtel’na, Andriy Pyrih, Danylo Shtoyko, Anna Susel, and Andrzej Gzella
Georg Thieme Verlag KG
Abstract Herein, we describe a one-pot, three-component method for the synthesis of 5-arylidene-4-aminothiazol-2(5H)-ones based on the reaction of isorhodanine, aromatic aldehydes, and ethanolamine. The one-pot procedure for chromeno[2,3-d]thiazol-2-one synthesis starting from 4-aminothiazol-2(5H)-one was proposed following the study of 5-(2-hydroxybenzylidene)-thiazolidinones. Structural features of the starting 4-thioxo-2-thiazolidinone, 4-aminothiazol-2(5H)-one, and target compounds are discussed.
Danylo Kaminskyy, Ivanna Subtel’na, Borys Zimenkovsky, Olexandr Karpenko, Andrzej Gzella, and Roman Lesyk
Bentham Science Publishers Ltd.
The synthesis and antitumor activity screening of 4-aminothiazol-2(5H)-one derivatives were performed. The absence of possible 4-amino-imino tautomerism of thiazolidinones-2 has been confirmed based on the study of the molecule structures. The existence of the alone amino-form was confirmed. An anticancer activity screening was performed within the Developmental Therapeutics Program (National Cancer Institute/NIH, USA). Tested compounds possess low to moderate anticancer activity (average values - 60 cancer cell lines assay) with significant selective action on certain cancer cell lines (CCRF-CEM and RPMI-8226/leukemia, U251/CNS cancer, RFX 393/renal cancer, OVCAR/ovarian cancer etc.). The advantage of 5-ylidene-4-R-amino derivatives in comparison with compounds with free amino group was shown. Some structure-activity findings, the comparison of target compounds with isomeric 5-ylidene-2-imino(amino)thiazol-4(5H)-ones, as well as COMPARE analysis were described. Among the tested compounds (Z)-5-(furan-2-ylmethylidene)-4-(4-chlorophenylamino)thiazol-2(5H)-one (IIIk) and (Z)-5-(4-diethylaminophenylmethylidene)-4-(4-hydroxy-5-isopropyl-2-methylphenylamino)thiazol-2(5H)-one (IIIp) possessed the highest levels of activity.
R. B. Lesyk, B. S. Zimenkovsky, D. V. Kaminskyy, A. P. Kryshchyshyn, D. Ya. Havryluk, D. V. Atamanyuk, I. Yu. Subtel'na, and D. V. Khyluk
Institute of Molecular Biology and Genetics (NAS Ukraine)
The aim was analysis of 4-thiazolidinones and related heterocyclic systems anticancer activity data and formation of some rational design directions of potential anticancer agents. Synthetic research carried out in Danylo Halytsky Lviv National Medical University (DH LNMU) allowed us to propose a whole number of new molecular design directions of biological active 4-thiazolidinones and related heterocyclic systems, as well as obtain directed library that numbers over 5000 of novel compounds. At the present time in vitro anticancer activity screening was carried out for more than 1000 compounds (US NCI protocol (Developmental Therapeutic Program), among them 167 compounds showed high antitumor activity level. For the purpose of optimization and rational design of highly active molecules with optimal «drug-like» characteristics and discovering of possible mechanism of action SAR, QSAR analysis and molecular docking were carried out. The ultimate aim of the project is creating of innovative synthetic drug with special mechanism of action and sufficient pharmacological and toxicological features. Some aspects of structure–act ivity relationships were determined and structure design directions were proposed. The series of active compounds with high anticancer activity and/or selectivity levels were selected.
Ivanna Subtel’na, Dmytro Atamanyuk, Ewa Szymańska, Katarzyna Kieć-Kononowicz, Borys Zimenkovsky, Olexandr Vasylenko, Andrzej Gzella, and Roman Lesyk
Elsevier BV