Fragment-Based Discovery of 5-Arylisatin-Based Inhibitors of Matrix Metalloproteinases 2 and 13статья
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Дата последнего поиска статьи во внешних источниках: 12 июля 2019 г.
Аннотация:Matrix metalloproteinases (MMPs) are well-established targets
for several pathologies. In particular, MMP-2 and MMP-13 play
a prominent role in cancer progression. In this study, a structure-
based screening campaign was applied to prioritize metalloproteinase-
oriented fragments. This computational model
was applied to a representative fragment set from the publically
available EDASA Scientific compound library. These fragments
were prioritized, and the top-ranking hits were tested in
a biological assay to validate the model. Two scaffolds showed
consistent activity in the assay, and the isatin-based compounds
were the most interesting. These latter fragments have
significant potential as tools for the design and realization of
novel MMP inhibitors. In addition to their micromolar activity,
the chemical synthesis affords flexible and creative access to
their analogues.