Antiproliferative effects of chalcones on T cell acute lymphoblastic leukemia‐derived cells: Role of PKCβ

Abstract

A series of twenty chalcone derivatives was synthetized and their anti-proliferative activity was tested against the human T-cell acute lymphoblastic leukemia-derived cell line (CCRF-CEM).Based on the structural features of the most active compounds a new library of chalcone derivatives, according to SAR design, was synthetized and their antiproliferative activity was tested on the same cancer cell line. Four of them (compounds 3, 4, 8, 28), based on lower IC50 values (between 6.1 and 8.9 M), were selected for further investigation regarding the modulation of the protein expression of receptor for activated C kinase (RACK1), PKCα and PKCβ, and their action at cell cycle level.Cell cycle analysis indicated a block in G0/G1 phase for all four compounds, with a statistically significant decrease in the percentage of cells in S phase, with no indication of apoptosis (subG0/G1 phase). Compounds 4 and 8 showed a statistical 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 antiproliferative effect observed is likely to be mediated through PKCβ induction.

Exploring the copper binding ability of Mets7 hCtr‐1 protein domain and His7 derivative: An insight in Michael addition catalysis

“…The catalytic performance of peptide–copper complexes was then investigated in the asymmetric Michael condensation of different substituted chalcones 47 with nitromethane. This reaction represents an important synthetic tool to form new C–C bonds, and it is commonly used for the obtainment of valuable synthetic intermediates.…”

Chemistry and synthetic methodologies of chalcones and their derivatives: A review

“…Like chalcones, coumarins, hydroxy coumarins, chalconoids and curcuminoids are also naturally occurring moieties with an α, β-unsaturated carbonyl system extending their potential towards cancer i.e., the compounds containing hydrazide-hydrazone, acrylonitrile and 2-amino-3-cyanopyridine moieties exhibited significant anticancer potential [20]. The chalcones and their derivatives were synthesized by using various synthetic strategies including Claisen-Schmidt condensation [21], Knoevenagel condensation [22], Microwave-assisted synthesis [23], Ultrasonic-assisted synthesis [24], stirring at high temperature [25], Refluxing [26], Molecular hybridization approach [27] and basecatalyzed condensation reaction [28]. Among the various approaches, the chalcones and their derivatives were highly synthesized by employing the Claisen-Schmidt condensation approach.…”

Effect of substituents in the A and B rings of chalcones on antiparasite activity

“…In search of antiparasitic drugs, several natural products have been previously reported. Particularly, chalcone-type compounds (1,3-diaryl-2-propen-1-one) exhibited activity against Leishmania species, [5][6][7][8][9] T. cruzi, [9,10] and P. falciparum, [11,12] in addition to antioxidant, cytotoxic, [10,13] antiproliferative, [14,15] antitumoral, [16,17] antimicrobial, [18] antiulcer, and anti-inflammatory activities, [19] among others. Thus, a wide range of synthetic procedures had been carried out to establish structure-activity relationships in these compounds, but the structure requirements involved in these activities are still practically unknown.…”

“…All compounds were more active than AMB.Only compounds 8, 10, 13, 16, and 17 showed high activity against T. cruzi, and the most powerful was 17, with EC 50 = 8.1 ± 1.1 µM, which was seven times more active than BNZ. A moderate activity against T. cruzi was observed in compounds 4,5,6,9,12,15,18,19,20, and 21, whose activity was higher than 20 µM, but lower than 50 µM. For compounds 3 and 7, it was not possible to determine the exact EC 50 values against T. cruzi, given its toxicity to U-937 host cells, whereas the remaining compounds, 1, 2, 11, and 14, exhibited a Hence, the discussion of the effects of the molecules will focus on the results exhibited on L. braziliensis and T. cruzi.…”