Simple item page
 

Anticancer cytotoxicity of indole-thiazolidinone hybrids, in silico study of mechanisms of their action

cris.virtual.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtual.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtual.author-orcid0000-0003-4057-7333
cris.virtual.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtual.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtual.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtual.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtualsource.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtualsource.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtualsource.author-orcidedaa3f24-c687-4516-93a8-b178493c02f0
cris.virtualsource.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtualsource.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtualsource.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtualsource.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
dc.abstract.enAim. The directed design and synthesis of new hybrid molecules containing [6+5]-heterocycles and thiazolidinone fragment, and their evaluation as potent anticancer agents. Methods. Organic synthesis, biological in vitro assays, SAR analysis, molecular docking, pharmacoph ore modelling. Results. A series of novel synthetic hybrid thiazolidinone-indole-carboxylates was designed, synthesized, and screened for their toxic activity towards the human hepatocar cinoma (HepG2), human glioblastoma (U251), human breast adenocarcinoma (MCF-7), and human promyelocytic leukemia (HL-60) cell lines. The lines of hepatocarcinoma, glioblas toma and breast adenocarcinoma were weakly sensitive to the studied compounds, the viabil ity of the human promyelocytic leukemia cell line HL-60 was inhibited by 5-fluoro-3-[2-(4 hydroxyanilino)-4-oxo-thiazol-5-ylidene]methyl]-1H-indole-2-carboxylate at the micromolar concentration IC50 = 8.36 μM. The cytotoxic action of this compound tested on a panel of cancer cell lines showed that the cell lines of leukemia, melanoma, and ovarian cancer were the most sensitive to it. Conclusions. The in vitro screening of biological effects of the syn thesized compounds allowed identifying a hit-compound 2c with high antileukemic action and low toxicity towards pseudonormal murine fibroblasts (Balb/c3T3). In general, 4-thiazolidinone indolecarboxylate 2c inhibited by >50 % the viability of 21 tumor cell lines. The in silico studies of putative binding mechanisms of the hit-compound 2c showed its high affinity to the colchicine site of cytoskeletal protein tubulin.
dc.affiliationWydział Medycyny Weterynaryjnej i Nauk o Zwierzętach
dc.affiliation.instituteKatedra Nauk Przedklinicznych i Chorób Zakaźnych
dc.contributor.authorKryshchyshyn-Dylevych, A. P.
dc.contributor.authorSubtelna, I. Y.
dc.contributor.authorFiniuk, N. S.
dc.contributor.authorRadko, Lidia
dc.contributor.authorPawełczyk, A.
dc.contributor.authorStoika, R. S.
dc.contributor.authorLesyk, R. B.
dc.date.access2026-01-12
dc.date.accessioned2026-01-12T07:36:54Z
dc.date.available2026-01-12T07:36:54Z
dc.date.copyright2022-09
dc.date.issued2022
dc.description.accesstimeat_publication
dc.description.bibliographyil., bibliogr.
dc.description.financepublication_nocost
dc.description.financecost0,00
dc.description.number4
dc.description.points20
dc.description.versionfinal_published
dc.description.volume38
dc.identifier.doi10.7124/bc.000A82
dc.identifier.eissn1993-6842
dc.identifier.issn0233-7657
dc.identifier.urihttps://sciencerep.up.poznan.pl/handle/item/6700
dc.identifier.weblinkhttps://biopolymers.org.ua/content/38/4/257/
dc.languageen
dc.relation.ispartofBiopolymers and Cell
dc.relation.pages257-277
dc.rightsCC-BY
dc.sciencecloudsend
dc.share.typeOPEN_JOURNAL
dc.subject.en1H-indole
dc.subject.enthiazolidine
dc.subject.ensynthesis
dc.subject.enanticancer activity
dc.subject.enSAR analysis
dc.subject.enin silico study
dc.titleAnticancer cytotoxicity of indole-thiazolidinone hybrids, in silico study of mechanisms of their action
dc.typeJournalArticle
dspace.entity.typePublication
oaire.citation.issue4
oaire.citation.volume38