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Synthesis, molecular docking and evaluation of novel sulfonyl hydrazones as anticancer agents and COX-2 inhibitors

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Abstract

In trying to develop new anticancer agents, a series of sulfonylhydrazones were synthesized. All synthesized compounds were checked for identity and purity using elemental analysis, TLC and HPLC and were characterized by their melting points, FT-IR and NMR spectral data. All synthesized compounds were evaluated for their cytotoxic activity against prostate cancer (PC3), breast cancer (MCF-7) and L929 mouse fibroblast cell lines. Among them, N′-[(2-chloro-3-methoxyphenyl)methylidene]-4-methylbenzenesulfonohydrazide (3k) showed the most potent anticancer activity against both cancer cells with good selectivity (IC50 = 1.38 μM on PC3 with SI = 432.30 and IC50 = 46.09 μM on MCF-7 with SI = 12.94). Further investigation confirmed that 3k displayed morphological alterations in PC3 and MCF-7 cells and promoted apoptosis through down-regulation of the Bcl-2 and upregulation of Bax expression. Additionally, compound 3k was identified as the most potent COX-2 inhibitor (91% inhibition) beside lower COX-1 inhibition. Molecular docking of the tested compounds represented important binding modes which may be responsible for their anticancer activity via inhibition of the COX-2 enzyme. Overall, the lead compound 3k deserves further development as a potential anticancer agent.

Graphic abstract

Sulfonylhydrazones was synthesized and N′-[(2-chloro-3-methoxyphenyl)methylidene]-4- methylbenzenesulfonohydrazide (3k) was identified as the most potent anticancer agent and COX-2 inhibitor. In addition, this compound docked inside the active site of COX-2 succesfully.

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Acknowledgements

This work was supported by the Research Fund of Marmara University, Project Number: SAG-K-120917-0495.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, Haydarpaşa, 34668, İstanbul, Turkey

    Sevil Şenkardeş, Necla Kulabaş, İlkay Küçükgüzel & Ş. Güniz Küçükgüzel

  2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Erciyes University, Kayseri, Turkey

    M. İhsan Han

  3. Scientific Technology Research and Application Centre, Adnan Menderes University, Aydın, Turkey

    Mürüvvet Abbak

  4. Department of Biochemistry, School of Medicine, Adnan Menderes University, Aydın, Turkey

    Özge Çevik

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  1. Sevil Şenkardeş
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Şenkardeş, S., Han, M.İ., Kulabaş, N. et al. Synthesis, molecular docking and evaluation of novel sulfonyl hydrazones as anticancer agents and COX-2 inhibitors. Mol Divers 24, 673–689 (2020). https://doi.org/10.1007/s11030-019-09974-z

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