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Novel 1,2,4-triazoles derived from Ibuprofen: synthesis and in vitro evaluation of their mPGES-1 inhibitory and antiproliferative activity

Molecular Diversity (2022)Cite this article

Abstract

Some novel triazole-bearing ketone and oxime derivatives were synthesized from Ibuprofen. In vitro cytotoxic activities of all synthesized molecules against five cancer lines (human breast cancer MCF-7, human lung cancer A549, human prostate cancer PC-3, human cervix cancer HeLa, and human chronic myelogenous leukemia K562 cell lines) were evaluated by MTT assay. In addition, mouse embryonic fibroblast cells (NIH/3T3) were also evaluated to determine the selectivity. Compounds 18, 36, and 45 were found to be the most cytotoxic, and their IC50 values were in the range of 17.46–68.76 µM, against the tested cancer cells. According to the results, compounds 7 and 13 demonstrated good anti-inflammatory activity against the microsomal enzyme prostaglandin E2 synthase-1 (mPGES-1) enzyme at IC50 values of 13.6 and 4.95 µM. The low cytotoxicity and non-mutagenity of these compounds were found interesting. Also, these compounds significantly prevented tube formation in angiogenesis studies. In conclusion, the anti-inflammatory and angiogenesis inhibitory activities of these compounds without toxicity suggested that they may be promising agents in anti-inflammatory treatment and they may be supportive agents for the cancer treatment.

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Funding

This work has been supported by Marmara University Scientific Research Projects Coordination Unit under grant number SAG-A-070617-0336.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Düzce University, Konuralp, Düzce, Turkey

    Bahadır Bülbül

  2. Department of Pharmaceutical Chemistry, Institute of Health Sciences, Marmara University, Dragos, Kartal, 34865, Istanbul, Turkey

    Bahadır Bülbül

  3. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA

    Kai Ding & Chang-Guo Zhan

  4. Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA

    Kai Ding & Chang-Guo Zhan

  5. Department of Bioinformatics and Genetics, Faculty of Engineering and Natural Sciences, Kadir Has University, Istanbul, Turkey

    Gamze Çiftçi & Kemal Yelekçi

  6. Department of Biochemistry, Faculty of Pharmacy, Marmara University, Haydarpaşa, 34668, Istanbul, Turkey

    Merve Gürboğa & Özlem Bingöl Özakpınar

  7. Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, Kayışdağı, Istanbul, Turkey

    Esra Aydemir, Deniz Baybağ & Fikrettin Şahin

  8. Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Biruni University, Zeytinburnu, 34010, Turkey

    Esra Aydemir

  9. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, Başıbüyük, 34854, Istanbul, Turkey

    Necla Kulabaş, Esra Tatar & İlkay Küçükgüzel

  10. Department of Toxicology, Faculty of Pharmacy, Yeditepe University, Ataşehir, 34750, Istanbul, Turkey

    Sinem Helvacıoğlu & Mohammad Charehsaz

  11. Department of Physics Engineering, Faculty of Engineering, Hacettepe University, Beytepe, 06800, Ankara, Turkey

    Süheyla Özbey

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  1. Bahadır Bülbül
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Bülbül, B., Ding, K., Zhan, CG. et al. Novel 1,2,4-triazoles derived from Ibuprofen: synthesis and in vitro evaluation of their mPGES-1 inhibitory and antiproliferative activity. Mol Divers (2022). https://doi.org/10.1007/s11030-022-10551-0

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Keywords

  • 1,2,4-Triazole
  • Atropisomer
  • Diastereotope
  • X-ray diffraction
  • Cancer
  • Angiogenesis
  • mPGES-1
  • Cytotoxicity