53744-32-4Relevant articles and documents
Promising Non-cytotoxic Monosubstituted Chalcones to Target Monoamine Oxidase-B
Iacovino, Luca G.,Pinzi, Luca,Facchetti, Giorgio,Bortolini, Beatrice,Christodoulou, Michael S.,Binda, Claudia,Rastelli, Giulio,Rimoldi, Isabella,Passarella, Daniele,Di Paolo, Maria Luisa,Dalla Via, Lisa
supporting information, p. 1151 - 1158 (2021/06/30)
A library of monosubstituted chalcones (1-17) bearing electron-donating and electron-withdrawing groups on both aromatic rings were selected. The cell viability on human tumor cell lines was evaluated first. The compounds unable to induce detectable cytotoxicity (1, 13, and 14) were tested using the monoamine oxidase (MAO) activity assay. Interestingly, they inhibit MAO-B, acting as competitive inhibitors, with 13 and 14 showing the best profiles. In particular, 13 exhibited a potency higher than that of safinamide, taken as a reference. Docking studies and crystallographic analysis showed that in human MAO-B 13 binds with the halogen-substituted aromatic ring in the entrance cavity, similar to safinamide, whereas 14 is accommodated in the opposite way. The main conclusion of this cell biology, biochemistry, and structural study is to highlights 13 as a chalcone derivative that is worth consideration for the development of novel MAO-B-selective inhibitors for the treatment of neurodegenerative diseases.
Antiproliferative effects of chalcones on T cell acute lymphoblastic leukemia-derived cells: Role of PKCβ
Corsini, Emanuela,Facchetti, Giorgio,Esposito, Sara,Maddalon, Ambra,Rimoldi, Isabella,Christodoulou, Michael S.
, (2020/05/16)
In this study, a series of 20 chalcone derivatives was synthesized, and their antiproliferative activity was tested against the human T cell acute lymphoblastic leukemia-derived cell line, CCRF-CEM. On the basis of the structural features of the most active compounds, a new library of chalcone derivatives, according to the structure–activity relationship design, was synthesized, and their antiproliferative activity was tested against the same cancer cell line. Furthermore, four of these derivatives (compounds 3, 4, 8, 28), based on lower IC50 values (between 6.1 and 8.9 μM), were selected for further investigation regarding the modulation of the protein expression of RACK1 (receptor for activated C kinase), protein kinase C (PKC)α and PKCβ, and their action on the cell cycle level. The cell cycle analysis indicated a block in the G0/G1 phase for all four compounds, with a statistically significant decrease in the percentage of cells in the S phase, with no indication of apoptosis (sub-G0/G1 phase). Compounds 4 and 8 showed a statistically significant reduction in the expression of PKCα and an increase in PKCβ, which together with the demonstration of an antiproliferative role of PKCβ, as assessed by treating cells with a selective PKCβ activator, indicated that the observed antiproliferative effect is likely to be mediated through PKCβ induction.
One-Pot Synthesis of Functionalized Carbazoles via a CAN-Catalyzed Multicomponent Process Comprising a C-H Activation Step
González, Juan F.,Rocchi, Damiano,Tejero, Tomás,Merino, Pedro,Menéndez, J. Carlos
supporting information, p. 7492 - 7502 (2017/07/26)
The microwave-promoted three-component reaction between o-nitrochalcones, primary amines and β-dicarbonyl compounds in the presence of Ce(IV) ammonium nitrate constitutes the first example of a multicomponent carbazole synthesis. This reaction furnishes highly substituted and functionalized carbazole derivatives via a double annulation process that generates two C-C and two C-N bonds, with water as the only side product. Mechanistically, this transformation has some unusual features that include an intramolecular coupled hydrogenation-dehydrogenation process, the functionalization of a C-H group by direct attack onto a nitrogen function and a CAN-catalyzed reduction via hydride transfer from ethanol. The mechanisms of these reactions were studied with the aid of computational techniques.
