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Synthesis, characterization, and bioactivity of new bisamidrazone derivatives as possible anticancer agents

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Abstract

A novel series of new di-(N-piperazin-1-yl)amidrazones and related congeners (3a–s) was synthesized by reaction of Nʹ,Nʺ-(biphenyl-4,4ʹ-diyl)-bis(2-oxopropanehydrazonoyl chloride) (2) with a selected set of secondary amines in basic media. Structures of the newly synthesized compounds were confirmed by elemental analysis and by various spectroscopic techniques such as 1H NMR, 13C NMR, 2D-NMR, and ESI-HRMS spectral data. Prepared compounds have been screened for antitumor activity against different cancer cell lines including breast cancer (MCF-7), colon cancer (Caco-2), and Leukemia (K562) cell lines using the tetrazolium dye 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay. Although with varying degrees, a significant growth inhibitory and cytotoxic effect was observed on all three cancer cell lines. Compounds 3a, 3b, 3c, 3d, and 3m, showed significant growth inhibitory and cytotoxic effect against the aforementioned cancer cell lines. Glide docking studies against PI3Kα demonstrated that some structural analogues accommodate PI3Kα kinase domain and bind to Ser774, Ala775, Glu798, Lys802, Tyr836, Val851, Asn853, Thr856, Gln859, Ser919, and Asp933. Additionally, part of the backbones of prepared compounds fit the pharmacophoric features of PI3Kα active inhibitors.

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Acknowledgements

Authors wish to thank the Deanship of Scientific Research at The University of Jordan for financial support.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, The University of Jordan, Amman, 11942, Jordan

    Malath A. Al-Qtaitat, Mustafa M. El-Abadelah, Kamal Sweidan, Salim S. Sabri & Mohammad S. Mubarak

  2. Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan

    Dima A. Sabbah

  3. Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman, 11942, Jordan

    Sanaa Bardaweel

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  1. Malath A. Al-Qtaitat
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  2. Mustafa M. El-Abadelah
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  3. Dima A. Sabbah
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  4. Sanaa Bardaweel
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  5. Kamal Sweidan
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  6. Salim S. Sabri
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  7. Mohammad S. Mubarak
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Correspondence to Mohammad S. Mubarak.

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Al-Qtaitat, M.A., El-Abadelah, M.M., Sabbah, D.A. et al. Synthesis, characterization, and bioactivity of new bisamidrazone derivatives as possible anticancer agents. Med Chem Res 27, 1419–1431 (2018). https://doi.org/10.1007/s00044-018-2158-0

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