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Antiaging activity, molecular docking, and prediction of percutaneous absorption parameters of quinoline–hydrazone hybrids

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Abstract

The application of antiaging agents can contribute to the prevention and control of skin photoaging. In the current research, nine quinoline–hydrazone hybrids were synthesized to obtain biologically active compounds as possible antiaging agents. The compounds were tested through a comprehensive in vitro evaluation of antielastase, anticollagenase, and antihyaluronidase activities along with the determination of their potential to quench reactive oxygen species (ROS) by the ORAC method. The selected hybrids were subsequently tested on human dermal fibroblasts (HDF) to reveal possible UVB photoprotective activity. The most potent antiaging protection of all the prepared compounds was shown by the trihydroxylated quinoline–hydrazones 5 and 9, which showed the best collagenase inhibition (IC50 = 39.4 and 45.6 µM, respectively). Compound 5 also showed activity against elastase and hyaluronidase (IC50 = 164.2 and 318.8 µM, respectively). The molecular docking results suggest that the difference of inhibition between 5 and 9 is principally attributed to the hydrogen bonds interactions in the residues His218 and His228, and Zn atom in collagenase, Val216 in elastase and Tyr75 in hyaluronidase. In addition, compounds 5 and 9 were able to significantly protect human skin cells from UVB radiation in vitro. These compounds significantly decreased UVB-induced MMP-1 and ROS production and inhibited the suppression of type I procollagen synthesis in cultured HDF. The in silico dermatopharmacokinetic parameters showed promising results. Therefore, our study presented promising results for antiaging drug discovery, focusing on quinoline–hydrazone hybrids as dual inhibitors of skin aging-related enzymes, antioxidants, and inhibitors of the biological effects of UVB irradiation.

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Acknowledgements

This investigation received financial support from Universidad de Antioquia, UdeA.

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Authors and Affiliations

  1. Grupo de Investigación en Sustancias Bioactivas, Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia, Calle 70 No., Medellín, 52-21, Colombia

    Edison Osorio & Karent Bravo

  2. Química de Plantas Colombianas, Instituto de Química, Universidad de Antioquia, Calle 70 No., Medellín, 52–21, Colombia

    Wilson Cardona, Andres Yepes & Juan C. Coa

  3. Facultad de Ciencias Naturales y Matemáticas, Universidad de Ibagué, Carrera 22 calle 67, Ibagué, Colombia

    Edison H. Osorio

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  1. Edison Osorio
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Osorio, E., Bravo, K., Cardona, W. et al. Antiaging activity, molecular docking, and prediction of percutaneous absorption parameters of quinoline–hydrazone hybrids. Med Chem Res 28, 1959–1973 (2019). https://doi.org/10.1007/s00044-019-02427-0

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