Title:Anticancer Potential of Novel Cinnamoyl Derivatives against U87MG and SHSY-5Y
Cell Lines
Volume: 24
Issue: 1
Author(s): Niki Gouleni, Annalisa Di Rienzo, Sena Oner, Ceren Karagöz, Mehmet Enes Arslan, Adil Mardinoglu, Hasan Turkez, Antonio Di Stefano, Stamatia Vassiliou*Ivana Cacciatore*
Affiliation:
- Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Athens, Greece
- Department of Pharmacy, "G. D’Annunzio" University of Chieti-Pescara, 66100, Chieti Scalo, CH, Italy
Keywords:
Anticancer drugs, cinnamic acid, glioblastoma, SHSY-5Y cells, U87MG cells, cinnamoyl derivatives.
Abstract:
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.
