Browsing by Author "Di Rienzo, Annalisa"

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Anticancer Potential of Novel Cinnamoyl Derivatives Against U87mg and SHSY-5Y Cell Lines
(Bentham Science Publishing Ltd, 2024) Gouleni, Niki; Di Rienzo, Annalisa; Oner, Sena; Karagoz, Ceren; Arslan, Mehmet Enes; Mardinoglu, Adil; Cacciatore, Ivana
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 mu g/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 mu g/mL) application resulted in nearly 86% and 84% cytotoxicity in the U87MG and the SHSY-5Y cell lines, respectively. Compound 2c (25 mu g/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.
Novel Styryl-Thiazole Hybrids as Potential Anti-Alzheimer's Agents
(Royal Society of Chemistry, 2023) Gouleni, Niki; Di Rienzo, Annalisa; Yilmaz, Ahmet; Selvitopi, Harun; Arslan, Mehmet Enes; Mardinoglu, Adil; Cacciatore, Ivana
In this study, combining the thiazole and cinnamoyl groups into the styryl-thiazole scaffold, a series of novel styryl-thiazole hybrids (6a-p) was rationally designed, synthesized, and evaluated by the multi-target-directed ligands strategy as potential candidates for the treatment of Alzheimer's disease (AD). Hybrids 6e and 6i are the most promising among the synthesized hybrids since they are able to significantly increase cell viabilities in A beta 1-42-exposed-human neuroblastoma cell line (6i at the concentration of 50 mu g mL-1 and 6e at the concentration of 25 mu g mL-1 resulted in similar to 34% and similar to 30% increase in cell viabilities, respectively). Compounds 6e and 6i exhibit highly AChE inhibitory properties in the experimental AD model at 375.6 +/- 18.425 mU mL-1 and 397.6 +/- 32.152 mU mL-1, respectively. Moreover, these data were also confirmed by docking studies and in vitro enzyme inhibition assays. Compared to hybrid 6e and according to the results, 6i also has the highest potential against A beta 1-42 aggregation with over 80% preventive activity. The in silico prediction of the physicochemical properties confirms that 6i possesses a better profile compared to 6e. Therefore, compound 6i presents a promising multi-targeted active molecular profile for treating AD considering the multifactorial nature of AD, and it is reasonable to deepen its mechanisms of action in an in vivo experimental model of AD. Novel styryl-thiazole hybrids (6a-p) was rationally designed, synthesized, and evaluated by the multi-target-directed ligands strategy as potential candidates for the treatment of Alzheimer's disease.