2,3-Dihydroquinazolin-4(1H)-one derivatives as potential non-peptidyl inhibitors of cathepsins B and H |
| |
Affiliation: | 1. Faculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, PO Box 5400, FIN-90014 Oulu, Finland;2. Department of Pharmacy at Birla Institute of Technology and Science-Pilani, Hyderabad campus, Hyderabad 500078, India;1. Key Laboratory of Auxiliary Chemistry & Technology for Chemical Industry, Ministry of Education, College of Chemistry & Chemical Engineering, Shaanxi University of Science & Technology, Xi''an, Shaanxi 710021, PR China;2. WuXi AppTec (Tianjin), Co., Ltd., TEDA, Tianjin 300457, PR China |
| |
Abstract: | A direct correlation between cathepsin expression–cancer progression and elevated levels of cathepsins due to an imbalance in cellular inhibitors-cathepsins ratio in inflammatory diseases necessitates the work on the identification of potential inhibitors to cathepsins. In the present work we report the synthesis of some 2,3-dihydroquinazolin-4(1H)-ones followed by their evaluation as cysteine protease inhibitors in general and cathepsin B and cathepsin H inhibitors in particular. 2,3-Dihydroquinazolin-4(1H)-ones, synthesized by the condensation of anthranilamide and carbonyl compound in presence of PPA-SiO2 catalyst, were characterized by spectral analysis. The designed compounds were screened as inhibitors to proteolysis on endogenous protein substrates. Further, a distinct differential pattern of inhibition was obtained for cathepsins B and H. The inhibition was more to cathepsin B with Ki values in nanomolar range. However, cathepsin H was inhibited at micromolar concentration. Maximum inhibition was shown by compounds, 1e and 1f for cathepsin B and compounds 1c and 1f for cathepsin H. The synthesized compounds were established as reversible inhibitors of cathepsins B and H. The results were also compared with the energy of interaction between enzyme active site and compounds using iGemdock software. |
| |
Keywords: | Cathepsin B Cathepsin H Non peptidyl inhibitors Endogenous proteolysis |
本文献已被 ScienceDirect 等数据库收录! |
|