AI Article Synopsis
- Cathepsin K (CatK) is a cysteine protease crucial for collagen breakdown and is targeted for treating bone disorders.
- This study introduces a green method for synthesizing new peptidomimetics using a one-pot epoxidation and Ugi reaction, which effectively inhibit CatK.
- The inhibitors showed selective action against CatK over cathepsin L, with a low micromolar inhibition profile, and further research indicated a mixed inhibition mechanism, enhancing our understanding of how these compounds interact with the enzyme.
Article Abstract
Cathepsin K (CatK) is a cysteine protease known for its potent collagenolytic activity, being recognized as an important target to the development of therapies for the treatment of bone disorders. Epoxypeptidomimetics have been reported as potent inhibitors of cathepsins, thus in this work we present a green synthesis of new peptidomimetics by using a one-pot asymmetric epoxidation/Ugi multicomponent reaction. The compounds were evaluated against CatK showing selectivity when compared with cathepsin L, with an inhibition profile in the low micromolar IC range. Investigation of the mechanism of action carried out for compounds LSPN428 and LSPN694 suggested a mixed inhibition mode and docking studies allowed a better understanding about interactions of inhibitors with the enzyme.
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| http://dx.doi.org/10.1016/j.bmc.2020.115597 | DOI Listing |
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