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Synthesis, characterization, and cytotoxic activity of some new 1,3,4-trisubstituted pyrazoles against diverse tumor cell lines

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Abstract

New derivatives of 1,3,4-trisubstituted pyrazole have been synthesized via different reaction routs starting with the chalcone (E)-3-[3-(4-bromophenyl)-1-ethyl-1H-pyrazol-4-yl]-1-(4-chlorophenyl)prop-2-en-1-one and dicarbonitrile 2-[[3-(4-bromophenyl)-1-ethyl-1H-pyrazol-4-yl]methylene]malononitrile derived from 3-(4-bromophenyl)-1H-pyrazole-4-carbaldehyde, and the in-vitro anti-cancer activity has been tested against various human cancer cell lines, namely: hepatocellular carcinoma HepG2, breast cancer MCF7, lung carcinoma A549, prostatic cancer PC3, and colon carcinoma HCT116. Some of the tested analogs exhibited significant activity on the target cell lines, and compound 4-[3-(4-bromophenyl)-1-ethyl-1H-pyrazol-4-yl]-1,2-dihydro-2-oxo-6-(pyridin-2-yl)pyridine-3-carbonitrile was not only the most potent among the tested compounds with IC50 = 9.130, 11.957, 9.130, 29.130, and 8.913 μM, compared with the reference standard doxorubicin (IC50 = 34.242, 20.851, 5.928, 38.024, 7.174 μM) on HepG2, MCF7, A549, PC3, and HCT116 cell lines, respectively, but also displayed no cytotoxic activity on the BJ-1 fibroblast normal human cell line. Objectively, the newly synthesized analogs can serve as a brick for the development of potent anti-cancer agents.

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Acknowledgements

We are grateful to National Research Centre, Cairo, Egypt for financial support under Project No. 11010312.

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Authors and Affiliations

  1. Department of Therapeutical Chemistry, National Research Centre, Dokki, Giza, 12622, Egypt

    Aladdin M. Srour, Hoda H. Fahmy & Mai A. Khater

  2. Pharmacognosy Department, National Research Centre, Dokki, Giza, 12622, Egypt

    May A. El-Manawaty

  3. X-Ray Crystallography Lab, Physics Division, National Research Centre, Dokki, Giza, 12622, Egypt

    ElSayed M. Shalaby

Authors
  1. Aladdin M. Srour
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  2. Hoda H. Fahmy
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  3. Mai A. Khater
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  4. May A. El-Manawaty
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  5. ElSayed M. Shalaby
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Correspondence to Aladdin M. Srour.

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Srour, A.M., Fahmy, H.H., Khater, M.A. et al. Synthesis, characterization, and cytotoxic activity of some new 1,3,4-trisubstituted pyrazoles against diverse tumor cell lines. Monatsh Chem 149, 1137–1147 (2018). https://doi.org/10.1007/s00706-018-2153-7

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