Synthesis of (Z)-3-((5-(benzylthio)-4H-1,2,4-triazol-3-yl)imino)-5-haloindolin-2-one derivatives: combined spectroscopic and computational investigations on the level and activity of matrix metalloproteinases 2 and 9 in cancer cell lines

Journal of the Iranian Chemical Society (2021)Cite this article

Abstract

Angiogenesis is an essential factor for cancer progression. Although more attention is paid in angiogenesis on its role in cancer biology, many other non-neoplastic diseases are also angiogenic-dependent. Recently, there is motivation to control cancer via inhibition of angiogenesis. Isatin-based scaffolds have been extensively used as anticancer agents in the recent years. Although some biological properties of isatin-based scaffolds are determined, their effects on angiogenesis are rare. So, we investigated the antiangiogenic effects of isatin-1,2,4-triazole conjugates. (Z)-3-((5-(benzylthio)-4H-1,2,4-triazol-3-yl)imino)-5-haloindolin-2-one macromolecules 1a–1l were synthesized and characterized, and the buffered solutions were used for evaluation of their cytotoxicity (cell viability) by MTT assay in vitro against U87MG (human glioblastoma astrocytoma) and A2780 (human ovarian carcinoma) cancer cell lines. Also, the effects of the compounds 1a–1l on supernatants activities and levels of matrix metalloproteinases (MMP-2 and MMP-9) were assayed using enzyme-linked immunosorbent assay (ELISA) and gelatin zymography. The compounds 1j–1l have the greatest cytotoxicity against studied cell lines. Moreover, our observations indicated that 1j–1l decreased the supernatants activity of MMP-2 and MMP-9 more than the others and all of the tested compounds considerably decreased the supernatant levels of MMP-9. The molecular mechanism of 1j binding to MMP-2 and MMP-9 was investigated by fluorescence quenching, absorption spectroscopy, FT-IR, molecular docking and molecular dynamics (MD) simulation procedures.

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Acknowledgements

We gratefully acknowledge Vice Chancellery for Research and Technology, Kermanshah University of Medical Sciences, for financial support (Grant No. 94071). This article resulted from the Pharm. D thesis of Mahdi Rahpeyma, Major of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.

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Affiliations

  1. Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Amir Kiani

  2. Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Mohsen Shahlaei

  3. Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Mahdi Rahpeyma

  4. Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Hadi Adibi

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  1. Amir Kiani
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  2. Mohsen Shahlaei
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Kiani, A., Shahlaei, M., Rahpeyma, M. et al. Synthesis of (Z)-3-((5-(benzylthio)-4H-1,2,4-triazol-3-yl)imino)-5-haloindolin-2-one derivatives: combined spectroscopic and computational investigations on the level and activity of matrix metalloproteinases 2 and 9 in cancer cell lines. J IRAN CHEM SOC (2021). https://doi.org/10.1007/s13738-020-02150-3

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Keywords

  • Isatin
  • 1,2,4-Triazole
  • Matrix metalloproteinases
  • Cytotoxic
  • Computational