Synthesis of new imidazo[1,2-a]pyridine triazole hybrid molecules as potential apoptotic antitumor agents

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dc.authorid0000-0003-0957-6965
dc.contributor.authorAlbayrak Halaç, Fatma
dc.contributor.authorEşsiz, Şebnem
dc.contributor.authorServili, Burak
dc.contributor.authorAltundaş, Ramazan
dc.contributor.authorOnur Sucu, Bilgesu
dc.contributor.authorKulu, İrem
dc.date.accessioned2024-03-08T06:36:34Z
dc.date.available2024-03-08T06:36:34Z
dc.date.issued2024
dc.departmentİstanbul Medipol Üniversitesi, Eczacılık Fakültesi, Eczacılık Meslek Bilimleri Bölümü, Farmasötik Kimya Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Sağlık Bilim ve Teknolojileri Araştırma Enstitüsü
dc.description.abstractNovel imidazo[1,2-a]pyridines bearing 1,2,3-triazole moieties at the C3 position were synthesized. After the characterization of the synthesized compounds, their in vitro therapeutic activities were evaluated in various cancer cell lines (MCF7, A549, HePG2 and T98G). Methoxy substituted derivative was identified as the most potent compound based on the results of its anti-proliferative activity on various cancer cell lines, as well as showing no cytotoxicity on the healthy human fibroblast cell line (MRC-5). As an indicator of apoptosis, a significant decrease in the level of PARP protein was observed in the MCF7 cells treated with this derivative. Molecular docking studies were conducted on wide range of targets such as phosphoinositide 3-kinase (PI3K), cyclin-independent kinase 2 (CDK2), mitogen-activated protein kinase (MEK), insulin-like growth-factor-1 (IGF-1), tubulin, DNA topoisomerase, poly (ADP-ribose) polymerase (PARP) and B-cell lymphoma-2 (BCL2). All the compounds tested showed the lowest binding energies with target PARP1. Moreover, CDK2 and tubulin displayed relatively good binding scores. The docking poses and scores were cross-checked with two different software and multiple protein conformations were included to incorporate flexible protein docking features. Finally, drug-likeness properties of the compounds are further tested via Swiss-ADME software. Novel imidazo[1,2-a]pyridine-1,2,3-triazole derivatives have been synthesized and evaluated for antiproliferative activity against MCF7, A549, HePG2, T98G cell lines. Compound 5c was found to be more potent on PARP protein in MCF7 cell line. The synthesized compounds were docked to PI3K, CDK2, MEK1, IGF-1, TUB1, DNA topoisomerase, PARP1, and BCL2. The best docking poses for PARP1 and CDK2 were obtained from 5c, 5d and 5 f. image
dc.identifier.citationAlbayrak Halaç, F., Eşsiz, Ş., Servili, B., Altundaş, R., Onur Sucu, B. ve Kulu, İ. (2024). Synthesis of new imidazo[1,2-a]pyridine triazole hybrid molecules as potential apoptotic antitumor agents. ChemistrySelect, 9(8). https://dx.doi.org/10.1002/slct.202304911
dc.identifier.doi10.1002/slct.202304911
dc.identifier.issn2365-6549
dc.identifier.issue8
dc.identifier.scopus2-s2.0-85185508092
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://dx.doi.org/10.1002/slct.202304911
dc.identifier.urihttps://hdl.handle.net/20.500.12511/12346
dc.identifier.volume9
dc.identifier.wos001169453500001en_US
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.institutionauthorOnur Sucu, Bilgesu
dc.language.isoen
dc.publisherJohn Wiley and Sons Inc
dc.relation.ispartofChemistrySelecten_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectMidazo[1,2-a]Pyridine
dc.subject1,2,3-Triazole
dc.subjectAnti-Proliferative
dc.subjectPARP
dc.subjectIn Silico Molecular Modeling
dc.titleSynthesis of new imidazo[1,2-a]pyridine triazole hybrid molecules as potential apoptotic antitumor agents
dc.typeArticle

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