Peptide-based targeted cancer therapeutics: Design, synthesis and biological evaluation

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creativework.keywordsCancer, In vitro testing, Molecular docking, Peptide drug design, Target therapy
creativework.publisherElsevier B.V.en
dc.contributor.authorIwanov I.
dc.contributor.authorRossi A.
dc.contributor.authorMontesi M.
dc.contributor.authorDoytchinova I.
dc.contributor.authorSargsyan A.
dc.contributor.authorMomekov G.
dc.contributor.authorPanseri S.
dc.contributor.authorNaydenova E.
dc.date.accessioned2024-07-10T14:27:05Z
dc.date.accessioned2024-07-10T14:50:10Z
dc.date.available2024-07-10T14:27:05Z
dc.date.available2024-07-10T14:50:10Z
dc.date.issued2022-09-01
dc.description.abstractCancer is the leading cause for human mortality together with cardiovascular diseases. Abl (Abelson) tyrosine kinases play a fundamental role in transducing various signals that control proliferation, survival, migration and invasion in several cancers such as Chronic Myeloid Leukemia (CML), breast cancer and brain cancer. For these reasons Abl tyrosine kinases are considered important biological targets in drug discovery. In this study a series of lysine-based oligopeptides with expected Abl inhibitory activity were designed resembling the binding of FDA-approved drugs (i.e. of Imatinib and Nilotinib), synthesized, purified by High Performance Liquid Chromatography (HPLC), analyzed by mass spectrometry (MS) and biologically tested in vitro in CML (AR-230 and K-562), breast cancers (MDA-MB 231 and MDA-MB 468) and glioblastoma cell lines (U87 and U118). The solid-phase peptide synthesis (SPPS) by Fmoc (9-fluorenylmethoxycarbonyl) chemistry was used to synthesize target compounds. AutoDock Vina was applied for simulation binding to Abl. The biological activities were measured evaluating cytotoxic effect, induction of apoptosis and inhibition of cancer cells migration. The new peptides exhibited different concentration-dependent antiproliferative effect against the tumor cell lines after 72 h treatment. The most promising results were obtained with the U87 glioblastoma cell line where a significant reduction of the migration ability was detected with one compound (H-Lys1-Lys2-Lys3-NH2).
dc.identifier.doi10.1016/j.ejps.2022.106249
dc.identifier.issn1879-0720
dc.identifier.issn0928-0987
dc.identifier.scopusSCOPUS_ID:85135501697en
dc.identifier.urihttps://rlib.uctm.edu/handle/123456789/733
dc.language.isoen
dc.source.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85135501697&origin=inward
dc.titlePeptide-based targeted cancer therapeutics: Design, synthesis and biological evaluation
dc.typeArticle
oaire.citation.volume176
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