Design and synthesis of novel caffeic acid phenethyl ester (CAPE) derivatives and their biological activity studies in glioblastoma multiforme (GBM) cancer cell lines

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dc.authorid0000-0003-0957-6965
dc.authorid0000-0003-1827-9540
dc.authorid0000-0002-9096-1512
dc.authorid0000-0002-1423-0435
dc.contributor.authorOnur Sucu, Bilgesu
dc.contributor.authorKoç, Elif Beyza
dc.contributor.authorŞavluğ İpek, Özgecan
dc.contributor.authorMirat, Afranur
dc.contributor.authorAlmas, Furkan
dc.contributor.authorGüzel, Melike Aybala
dc.contributor.authorDoğan, Berna
dc.contributor.authorUludağ, Damla
dc.contributor.authorKarakaş, Nihal
dc.contributor.authorDurdağı, Serdar
dc.contributor.authorGüzel, Mustafa
dc.date.accessioned2022-03-16T07:23:17Z
dc.date.available2022-03-16T07:23:17Z
dc.date.issued2022
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Sağlık Bilim ve Teknolojileri Araştırma Enstitüsü
dc.departmentİstanbul Medipol Üniversitesi, Sağlık Hizmetleri Meslek Yüksekokulu, Tıbbi Laboratuvar Teknikleri Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyoloji Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Sağlık Bilimleri Enstitüsü, Moleküler Tıp ve Biyoteknoloji Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Tıbbi Farmakoloji Ana Bilim Dalı
dc.description.abstractGlioblastoma Multiforme (GBM) is the most aggressive brain tumor and classified as one of the deadliest cancers. The current treatment plans for GBM remains to be ineffective because of its rapid progress and inability of the drugs used to cross the blood-brain barrier (BBB). Thus, developing more effective and potent medicines for GBM are needed. There have been several reports demonstrating that CAPE presents reasonably good anti-cancer activity in certain cancer cell lines and can penetrate the blood-brain barrier. Accordingly, in this study we synthesized several novel CAPE analogs with the addition of more druggable handles and solubilizing entities and subsequently evaluated their in vitro therapeutic efficacies in GBM cell lines (T98G and LN229). The most potent compound was then examined extensively and results showed that the 50 ?M novel CAPE analog (compound 10) significantly decreases the viability of both T98G and LN229 GBM cells as compared to CAPE itself. Moreover, the compound 10 was not cytotoxic to healthy human cells (fibroblast-like mesenchymal stem cells) at the same concentration. Apoptotic (32.8%, and 44.6%) cell populations were detected in the compound 10 treated groups for LN229 and T98G, respectively. As an indication of apotosis, significantly increased PARP cleavage was detected in compound 10 versus CAPE treated LN229. In addition, we conducted molecular docking and molecular dynamics (MD) simulations studies on certain targets playing roles on GBM disease pathway such as NF-?B, EGFR, TNF-?, ERK2, PAPR1, hCA IX and hCA XII. Our findings demonstrated that designed CAPE analogs have anti-cancer activity on GBM cells and in silico studies also demonstrate the inhibitory ability of suggested compounds via interactions with critical residues in binding pockets of studied targets. Here, we suggest the novel CAPE analog to study further against GBM. Therefore, identification of the compound related molecular signature may provide more to understand the mechanism of action.
dc.identifier.citationOnur Sucu, B., Koç, E. B., Şavluğ İpek, Ö. Mirat, A. Almas, F., Güzel, M. A. ... Güzel, M. (2022). Design and synthesis of novel caffeic acid phenethyl ester (CAPE) derivatives and their biological activity studies in glioblastoma multiforme (GBM) cancer cell lines. Journal of Molecular Graphics and Modelling, 113. https://doi.org/10.1016/j.jmgm.2022.108160
dc.identifier.doi10.1016/j.jmgm.2022.108160
dc.identifier.issn1873-4243
dc.identifier.issn1093-3263
dc.identifier.pmid35248814
dc.identifier.scopus2-s2.0-85125617762
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://doi.org/10.1016/j.jmgm.2022.108160
dc.identifier.urihttps://hdl.handle.net/20.500.12511/9120
dc.identifier.volume113
dc.identifier.wos000783091900003en_US
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorOnur Sucu, Bilgesu
dc.institutionauthorKoç, Elif Beyza
dc.institutionauthorŞavluğ İpek, Özgecan
dc.institutionauthorMirat, Afranur
dc.institutionauthorAlmas, Furkan
dc.institutionauthorGüzel, Melike Aybala
dc.institutionauthorUludağ, Damla
dc.institutionauthorKarakaş, Nihal
dc.institutionauthorGüzel, Mustafa
dc.language.isoen
dc.publisherElsevier Inc.
dc.relation.ispartofJournal of Molecular Graphics and Modellingen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectAnti-Cancer Activity
dc.subjectCaffeic Acid Phenethyl Ester (CAPE)
dc.subjectGlioblastoma Multiforme (GBM)
dc.subjectIn Silico Molecular Modeling
dc.subjectNovel Heterocyclic CAPE Analogs
dc.titleDesign and synthesis of novel caffeic acid phenethyl ester (CAPE) derivatives and their biological activity studies in glioblastoma multiforme (GBM) cancer cell lines
dc.typeArticle

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