Green asymmetric synthesis of epoxypeptidomimetics and evaluation as human cathepsin K inhibitors.

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 IC50 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.

New cathepsin V inhibitor from stems of Bowdichia virgilioides

Abstract Bioassay-guided fractionation of Bowdichia virgilioides Kunth, Fabaceae, extracts has led to the isolation of cathepsin V inhibitors. The investigation of the hexane and ethyl acetate extracts allowed the characterization of eleven compounds: lupeol, lupenone, β-sitosterol and stigmasterol in mixture, trans p-coumaric acid ester derivative, syringaresinol, bowdenol, 8-methoxycoumestrol, 3,4-hydroxy-7-methoxyisoflavone, 7,3′-dihydroxy-4′-methoxyisoflavone, and 5,4′-dihydroxy-7′-methoxyisoflavone. Structures of compounds were stablished by 1D and 2D NMR, and MS experiments. Among the isolated compounds, trans p-coumaric acid ester derivative and 8-methoxycoumestrol showed significant inhibition on cathepsin V, which is up to now unexplored.