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Hypolipidemic effect of novel 2,5-bis(4-hydroxybenzylidenamino)-1,3,4-thiadiazole as potential peroxisome proliferation-activated receptor-α agonist in acute hyperlipidemic rat model

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Abstract

The development of new antihyperlipidemic agents with higher potency and lower side effects is of high priority. In this study, 1,3,4 thiadiazole Schiff base derivatives were synthesized as potential peroxisome proliferation-activated receptor-α (PPARα) agonists and characterized using elemental analysis, FTIR, 1H-NMR, 13C-NMR and mass spectroscopy and then tested for their hypolipidemic activity in Triton WR-1339-induced acute hyperlipidemic rat model in comparison with bezafibrate. The compounds showed significant hypolipidemic activity. Induced fit docking showed that the compounds are potential activators of PPARα with binding scores − 8.00 Kcal/mol for 2,5-bis(4-hydroxybenzylidenamino)-1,3,4-thiadiazole. PCR array analysis showed an increase in the expression of several genes involved in lipid metabolism through mitochondrial fatty acid β oxidation and are part of PPARα signaling pathway including Acsm3, Fabp4 and Hmgcs1. Gene expression of Lrp12 and Lrp1b involved in LDL uptake by liver cells and Cyp7a1 involved in cholesterol catabolism were also found to be upregulated.

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Acknowledgements

The authors would like to thank Al-Zaytoonah University of Jordan for the financial support.

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Authors and Affiliations

  1. Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan

    Lama A. Hamadneh, Dima A. Sabbah, Suhair J. Hikmat, Luma A. Al-Samad, Mariam Hasan & Tariq M. Al-Qirim

  2. Department of Chemistry, Faculty of Science, University of Jordan, Amman, Jordan

    Imad M. Hamadneh

  3. Hamdi Mango Center for Scientific Research, University of Jordan, Amman, Jordan

    Imad M. Hamadneh & Ammar H. Al-Dujaili

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  1. Lama A. Hamadneh
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Correspondence to Lama A. Hamadneh.

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Hamadneh, L.A., Sabbah, D.A., Hikmat, S.J. et al. Hypolipidemic effect of novel 2,5-bis(4-hydroxybenzylidenamino)-1,3,4-thiadiazole as potential peroxisome proliferation-activated receptor-α agonist in acute hyperlipidemic rat model. Mol Cell Biochem 458, 39–47 (2019). https://doi.org/10.1007/s11010-019-03528-5

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