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

Edison Osorio, Karent Bravo, Wilson Cardona, Andres Yepes, Edison H. Osorio, Juan C. Coa

Resultado de la investigación: Contribución a una revistaArtículo

Resumen

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.

Idioma originalInglés
PublicaciónMedicinal Chemistry Research
DOI
EstadoAceptada/en prensa - 1 nov 2019

Huella dactilar

Skin Absorption
Skin Aging
Skin
Hyaluronoglucosaminidase
Pancreatic Elastase
Collagenases
Fibroblasts
Inhibitory Concentration 50
Reactive Oxygen Species
Enzyme Inhibitors
Drug Discovery
Collagen Type I
Matrix Metalloproteinases
Computer Simulation
Hydrogen
Hydrogen bonds
Antioxidants
Aging of materials
Irradiation
Radiation

Citar esto

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title = "Antiaging activity, molecular docking, and prediction of percutaneous absorption parameters of quinoline–hydrazone hybrids",
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.",
keywords = "Antiaging, Human dermal fibroblasts, Matrix metalloproteinase, Quinoline–hydrazone hybrids, UVB photoprotection",
author = "Edison Osorio and Karent Bravo and Wilson Cardona and Andres Yepes and Osorio, {Edison H.} and Coa, {Juan C.}",
year = "2019",
month = "11",
day = "1",
doi = "10.1007/s00044-019-02427-0",
language = "Ingl{\'e}s",
journal = "Medicinal Chemistry Research",
issn = "1054-2523",
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Antiaging activity, molecular docking, and prediction of percutaneous absorption parameters of quinoline–hydrazone hybrids. / Osorio, Edison; Bravo, Karent; Cardona, Wilson; Yepes, Andres; Osorio, Edison H.; Coa, Juan C.

En: Medicinal Chemistry Research, 01.11.2019.

Resultado de la investigación: Contribución a una revistaArtículo

TY - JOUR

T1 - Antiaging activity, molecular docking, and prediction of percutaneous absorption parameters of quinoline–hydrazone hybrids

AU - Osorio, Edison

AU - Bravo, Karent

AU - Cardona, Wilson

AU - Yepes, Andres

AU - Osorio, Edison H.

AU - Coa, Juan C.

PY - 2019/11/1

Y1 - 2019/11/1

N2 - 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.

AB - 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.

KW - Antiaging

KW - Human dermal fibroblasts

KW - Matrix metalloproteinase

KW - Quinoline–hydrazone hybrids

KW - UVB photoprotection

UR - http://www.scopus.com/inward/record.url?scp=85071507151&partnerID=8YFLogxK

U2 - 10.1007/s00044-019-02427-0

DO - 10.1007/s00044-019-02427-0

M3 - Artículo

AN - SCOPUS:85071507151

JO - Medicinal Chemistry Research

JF - Medicinal Chemistry Research

SN - 1054-2523

ER -