Abstract
Glycosidases, including β-d-galactosidase and β-d-glucosidase, are involved in a range of metabolic disorders, such as cancer, viral or bacterial infections, and diabetes. Previously, we scanned the pharmacophoric space of these enzymes and had a self-consistent and predictive quantitative structure–activity relationship that was used to identify several β-d-galactosidase and β-d-glucosidase inhibitors via in silico search of structural databases. Guided by the preceding modeling efforts, synthesis of a series of tryptophan and thiosemicarbazide derivatives as β-d-galactosidase and β-d-glucosidase inhibitors that match the generated pharmacophores followed by in vitro bioassay was carried out. Synthesized compounds 3c (37 % inhibition at 100 µM) and 4d (49 % inhibition at 100 µM) exhibited the best inhibitory bioactivities against β-d-galactosidase and β-d-glucosidase, respectively. They can serve as a promising lead compounds for the development of potential glycosidase inhibitors.
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Acknowledgments
We are grateful to the Deanship of Scientific Research and Hamdi-Mango Center for Scientific Research at the University of Jordan for their generous funds.
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Abu Khalaf, R., Abdula, A.M., Mubarak, M.S. et al. Tryptophan and thiosemicarbazide derivatives: design, synthesis, and biological evaluation as potential β-d-galactosidase and β-d-glucosidase inhibitors. Med Chem Res 24, 2529–2550 (2015). https://doi.org/10.1007/s00044-014-1314-4
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DOI: https://doi.org/10.1007/s00044-014-1314-4