Anticancer activity of novel 3‐(furan‐2‐yl)pyrazolyl and 3‐(thiophen‐2‐yl)pyrazolyl hybrid chalcones: Synthesis and in vitro studies

Abstract

Twelve novel chalcone derivatives were prepared using the Claisen–Schmidt condensation reaction. The reaction of 4‐acetyl‐5‐furan/thiophene‐pyrazole derivatives 5 with the corresponding aldehydes 6 afforded the targeted chalcone derivatives 7a–l in good yields. The newly synthesized chalcones were fully characterized by spectrometric and elemental analyses. The in vitro anticancer activities of the novel compounds 7a–l were evaluated against four human cancer cell lines: HepG2 (human hepatocellular carcinoma), MCF7 (human Caucasian breast adenocarcinoma), A549 (lung carcinoma), and BJ1 (normal skin fibroblasts). Compound 7g emerged as the most promising compound, with IC50 = 27.7 µg/ml against A549 cells compared to the reference drug doxorubicin (IC50 = 28.3 µg/ml), and IC50 = 26.6 µg/ml against HepG2 cells compared to the reference drug doxorubicin (IC50 = 21.6 µg/ml). The gene expression and DNA damage values and the DNA fragmentation percentages for compound 7g were determined on the lung and liver cell lines. The expression levels of the AMY2A and FOXG1 genes increased significantly (p < 0.01) in the negative samples of lung cancer cells compared with treated cells. Also, the expression values of the PKM and PSPH genes improved significantly (p < 0.01) in the negative samples compared with treated samples of liver cancer cells. The DNA damage values increased significantly (p < 0.01) in treated lung cell line samples (7g) and the positive control. The results showed a significant decrease (p < 0.05) in DNA damage values in the negative samples of liver cancer cells compared to those treated with 7g. However, the DNA fragmentation values increased significantly (p < 0.01) in the treated lung and liver cell line samples compared with the negative control.

Theoretical and molecular mechanistic investigations of novel (3-(furan-2-yl)pyrazol-4-yl) chalcones against lung carcinoma cell line (A549)

“…In addition, 3-(furan-2-yl)-1H-pyrazoles (Andicsová et al 2018;Ryan et al 2020;Barus et al 2021) have been reported to have biologically interesting applications. Based on these findings, and in continuation of our study interest in bioactive heterocycle production (Mohamed et al 2017, 2021a, b, c, Sroor et al 2019Fathi et al 2021;Helmy et al 2021;Ragheb et al 2022;Salem et al 2022;Waly Eldeen et al 2022), we were inspired to synthesize the pyrazolyl-chalcones and evaluate their in vitro anti-cancer effectiveness against different human cancer cell lines with an emphasis on the novel two chalcones 7b, and 7c that proved strong and interesting cytotoxic effect against lung carcinoma (A549) cell line. To find their effect on the apoptotic process of cancer cells, many theoretical and experimental investigations were extensively performed.…”

Synthesis, In-vitro antibacterial and antioxidant activity of chalcone derivatives

“…respectively. The 1 H-NMR and 13 C-NMR spectra of these synthesized chalcones are represented in the figures 2 and 3. 2.…”

“…They are widely distributed in nature (in plants, bacteries, fungi, etc.) and are generally synthesized in the Laboratory from aromatic aldehydes and aliphatic aldehydes or ketones via the condensation reaction Claisen-Schmidt in the presence of base or acid catalysts [11][12][13]. Chalcones have several biological activities such as antibacterial, antioxidant, anti-inflammatory, antiviral, antifungal, anti-ulceral, antimalarial, antileishmanial, anticancer, antitubercular, antihyperglycemic, anti-HIV, carboxygenase inhibitor, insecticidal, ect.…”

“…Figure2(a)1 H NMR and (b)13 C NMR of (E)-1-(2-hydroxyphenyl)-3-(4-hydroxyphenyl) prop-2-en-1-one1 H-NMR spectrum of these three synthesized chalcones (1,2, and 3) each revealed the singlet at δ 12.96; 12.94 and 12.99 ppm, respectively. This corresponds to the proton of the hydroxyl group close to the carbonyl group which is shielded and this difference could be due to the presence of the OH group in the other benzene cycle of the first synthetic chalcone, either the methoxy group OCH3 in the second chalcone or the two methoxy (OCH3) groups in the other benzene of the third synthesized chalcone.…”

Synthesis and Characterization of Novel Heterocyclic Chalcones from 1-Phenyl-1H-pyrazol-3-ol

“…Chalcones are usually synthesized from aromatic aldehydes and aliphatic aldehydes or ketones via the Claisen-Schmidt condensation reaction in the presence of base or acid catalysts [19][20][21][22]. Other procedures were efficiently employed for the synthesis of chalcones, including the Pd-catalysed Suzuki cross-coupling reaction between the appropriate Molecules 2022, 27, 3752 2 of 32 cinnamoyl chloride and phenylboronic acid or benzoyl chloride and phenylvinylboronic acid or Heck coupling reaction between aryl iodide and an unsaturated ketone [23][24][25].…”