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Structure-based design of novel pyrazolyl–chalcones as anti-cancer and antimicrobial agents: synthesis and in vitro studies

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Abstract

A new series of pyrazolyl–chalcone derivatives was prepared in moderate yields via Claisen–Schmidt condensation reaction of 4-acetylpyrazole derivatives with the corresponding aldehydes. The newly synthesized compounds have been fully characterized by 1H NMR, 13C NMR, IR, mass spectrometry, and elemental analysis. The in vitro antimicrobial and anti-cancer activities of the novel compounds were evaluated. Depending on the structure of the molecule, different types of compounds have varying effects on microbial growth effectiveness. 3-(2,4-Dimethoxyphenyl)-1-[3,5-dimethyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl]prop-2-en-1-one gave the highest antibacterial activity (20 mm) against B. mycoides, whereas 3-(4-chlorophenyl)-1-[3,5-dimethyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl]prop-2-en-1-one and 1-[3,5-dimethyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl]-3-(p-tolyl)prop-2-en-1-one had equivalent antibacterial activity (17 mm) against E. coli. The 4-chlorophenyl derivative exhibited the most potent antifungal activity against C. albicans (17 mm). The anti-cancer activity of the prepared compounds was tested against four human cancer cell lines namely A549 (lung carcinoma), MCF7 (human caucasian breast adenocarcinoma), HePG2 (human hepatocellular carcinoma cell line), and BJ1 (normal skin fibroblast). 1-[3,5-Dimethyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl]-3-(p-tolyl)prop-2-en-1-one emerged as the most promising compound with IC50 = 44.3 µg/cm3 against A549 and IC50 = 57.9 µg/cm3 against HePG2. Its gene expression, DNA damage values, and DNA fragmentation percentages have been discussed. The expression values of ISL1 and MALL, ASNS and ACLY genes were decreased significantly in treated lung and liver cell lines respectively and positive control compared with negative samples. The expression levels of ISL1 and MALL genes were downregulated in positive control lung cell lines much lower than those in the p-tolyl substituted derivative. The expression levels of ASNS and ACLY genes were downregulated similar to those in positive control liver cell lines. The DNA damage values and DNA fragmentation percentages were increased significantly (P < 0.01) in the treated lung and liver sample compared with the negative control.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt

    Monica G. Kamel, Fatma M. Saleh, Hamdi M. Hassaneen, Tayseer A. Abdallah, Ismail A. Abdelhamid & Mohamed A. Mohamed Teleb

  2. Organometallic and Organometalloid Chemistry Department, National Research Centre, Cairo, 12622, Egypt

    Farid M. Sroor

  3. Institut Für Anorganische Chemie, Universität Göttingen, Tammannstrasse 4, 37077, Göttingen, Germany

    Farid M. Sroor

  4. Microbial Chemistry Department, Biotechnology Research Institute, National Research Centre, Dokki, Giza, 12622, Egypt

    Abdelmageed M. Othman

  5. Cell Biology Department, National Research Centre, Dokki, Giza, 12622, Egypt

    Karima F. Mahrous

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  1. Monica G. Kamel
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Kamel, M.G., Sroor, F.M., Othman, A.M. et al. Structure-based design of novel pyrazolyl–chalcones as anti-cancer and antimicrobial agents: synthesis and in vitro studies. Monatsh Chem 153, 211–221 (2022). https://doi.org/10.1007/s00706-021-02886-5

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  • DOI: https://doi.org/10.1007/s00706-021-02886-5

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