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

  • Sevil ŞenkardeşEmail author
  • M. İhsan Han
  • Necla Kulabaş
  • Mürüvvet Abbak
  • Özge Çevik
  • İlkay Küçükgüzel
  • Ş. Güniz Küçükgüzel
Original Article

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.

Keywords

Anticancer activity Apoptosis Cyclooxygenase Molecular docking Sulfonylhydrazones 

Notes

Acknowledgements

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

Compliance with ethical standards

Conflict of interest

The authors have declared no conflict of interest.

Supplementary material

11030_2019_9974_MOESM1_ESM.xlsx (121 kb)
Supplementary material 1 (XLSX 120 kb)

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutical Chemistry, Faculty of PharmacyMarmara UniversityİstanbulTurkey
  2. 2.Department of Pharmaceutical Chemistry, Faculty of PharmacyErciyes UniversityKayseriTurkey
  3. 3.Scientific Technology Research and Application Centre, Adnan Menderes UniversityAydınTurkey
  4. 4.Department of Biochemistry, School of MedicineAdnan Menderes UniversityAydınTurkey

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