Anticancer Potential of Novel Cinnamoyl Derivatives against U87MG and SHSY-5Y Cell Lines


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Background:Glioblastoma multiforme (GBM) is probably the most malignant and aggressive brain tumor belonging to the class of astrocytomas. The considerable aggressiveness and high malignancy of GBM make it a tumor that is difficult to treat. Here, we report the synthesis and biological evaluation of eighteen novel cinnamoyl derivatives (3a-i and 4a-i) to obtain more effective antitumor agents against GBM.

Methods:The chemical structures of novel cinnamoyl derivatives (3a-i and 4a-i) were confirmed by NMR and MS analyses. The physicochemical properties and evaluation of the ADME profile of 3a-i and 4a-i were performed by the preADMETlab2.0 web program. Cinnamoyl derivatives 3a-i and 4a-i were tested in vitro for their cytotoxicity against the human healthy fibroblast (HDFa) cells using an MTT cell viability assay. Derivatives with no toxicity on HDFa cells were tested both on human glioblastoma (U87MG) and neuroblastoma (SHSY- 5Y) cells, chosen as an experimental model of brain tumors. Cell death mechanisms were analyzed by performing flow cytometry analyses.

Results:Cinnamoyl derivatives 3a-i and 4a-i showed good physicochemical and ADME properties suggesting that these compounds could be developed as oral drugs endowed with a high capability to cross the blood-brain barrier. Compounds (E)-1-methoxy-4-(2-(phenylsulfonyl)vinyl)benzene (2c) and (E)-N-benzyl-N-(2- (cyclohexylamino)-2-oxoethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide (3e) did not show cytotoxicity on healthy human fibroblast cells up to 100 µg/mL. The most anticarcinogenic molecule, compound 3e, emerged as the most potent anticancer candidate in this study. Flow cytometry results showed that compound 3e (25 µg/mL) application resulted in nearly 86% and 84% cytotoxicity in the U87MG and the SHSY-5Y cell lines, respectively. Compound 2c (25 µg/mL) resulted in 81% and 82% cytotoxicity in the U87MG and the SHSY-5Y cell lines, respectively.

Conclusion:Cinnamoyl derivative 3e inhibits the proliferation of cultured U87MG and SHSY-5Y cells by inducing apoptosis. Further detailed research will be conducted to confirm these data in in vivo experimental animal models.

Об авторах

Niki Gouleni

Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens

Email: info@benthamscience.net

Annalisa Di Rienzo

Department of Pharmacy,, "G. D’Annunzio" University of Chieti-Pescara

Email: info@benthamscience.net

Sena Oner

Department of Molecular Biology and Genetics, Faculty of Science,, Erzurum Technical University

Email: info@benthamscience.net

Ceren Karagöz

Department of Molecular Biology and Genetics, Faculty of Science,, Erzurum Technical University

Email: info@benthamscience.net

Mehmet Arslan

Department of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University

Email: info@benthamscience.net

Adil Mardinoglu

Science for Life Laboratory,, KTH-Royal Institute of Technology,

Email: info@benthamscience.net

Hasan Turkez

Department of Medical Biology, Faculty of Medicine,, Atatürk University

Email: info@benthamscience.net

Antonio Di Stefano

Department of Pharmacy, "G. D’Annunzio" University of Chieti-Pescara,

Email: info@benthamscience.net

Stamatia Vassiliou

Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens

Автор, ответственный за переписку.
Email: info@benthamscience.net

Ivana Cacciatore

Department of Pharmacy,, "G. D’Annunzio" University of Chieti-Pescara

Автор, ответственный за переписку.
Email: info@benthamscience.net

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